Procalcitonin and cellulitis: correlation of procalcitonin blood levels with measurements of severity and outcome in patients with limb cellulitis.

BACKGROUND: Procalcitonin levels may be raised in bacterial infections and have been used to guide antibiotic therapy. There is little data on procalcitonin and limb cellulitis. OBJECTIVES: Within a clinical trial of antibiotic therapy, we examined the correlation between clinical observations, blood tests and local measurements of skin damage, with serum procalcitonin levels. METHODS: The data is from a subset of the patients recruited into a clinical trial of antibiotic therapy for cellulitis (clindamycin for cellulitis, NCT01876628) whose procalcitonin levels were correlated with clinical and laboratory measurements. We selected the variables strongly correlated with procalcitonin and evaluated the predictive value of the baseline procalcitonin on the primary trial outcome. RESULTS: 136 patients provided 307 procalcitonin levels which were correlated with 8 variables. The strongest correlations (correlation coefficient of >0.5) with procalcitonin were the affected skin area (0.537), C-reactive protein (0.574) and neutrophil:lymphocyte ratio (0.567). Receiver operator characteristic curves demonstrated poor sensitivity and specificity of procalcitonin in predicting primary outcome. Procalcitonin baseline levels were low but decreased as patients recovered. CONCLUSIONS: Procalcitonin levels are generally low in limb cellulitis and cannot be used to confirm the diagnosis or the need for antibiotic therapy. Procalcitonin is a poor predictor of early improvement.

Acute management of cellulitis: A review.

Cellulitis is an acute localised skin infection, usually accompanied by symptoms such as fever and rigors, nausea, and vomiting. It most commonly affects the lower limbs, although it can involve any part of the skin. It presents as area of redness and inflammation of the skin, with associated pain and swelling.

Cardiovascular reactivity patterns and pathways to hypertension: a multivariate cluster analysis.

Substantial evidence links exaggerated mental stress induced blood pressure reactivity to future hypertension, but the results for heart rate reactivity are less clear. For this reason multivariate cluster analysis was carried out to examine the relationship between heart rate and blood pressure reactivity patterns and hypertension in a large prospective cohort (age range 55-60 years). Four clusters emerged with statistically different systolic and diastolic blood pressure and heart rate reactivity patterns. Cluster 1 was characterised by a relatively exaggerated blood pressure and heart rate response while the blood pressure and heart rate responses of cluster 2 were relatively modest and in line with the sample mean. Cluster 3 was characterised by blunted cardiovascular stress reactivity across all variables and cluster 4, by an exaggerated blood pressure response and modest heart rate response. Membership to cluster 4 conferred an increased risk of hypertension at 5-year follow-up (hazard ratio=2.98 (95% CI: 1.50-5.90), P<0.01) that survived adjustment for a host of potential confounding variables. These results suggest that the cardiac reactivity plays a potentially important role in the link between blood pressure reactivity and hypertension and support the use of multivariate approaches to stress psychophysiology.

Comparative humoral responses to HIV-1 p24gag and gp120env in subjects from East Africa and the UK.

We compared 1616 sera from HIV-1-infected subjects and matched HIV-negative local controls in Uganda, Kenya and the UK. Sera were screened for specific antibody to HIV-1 p24 Gag and gp120 Env proteins and for p24 antigenaemia. In contrast to the UK, the majority of African HIV-1-infected subjects maintained detectable anti-p24 antibodies. However, lower reactivity of anti-p24 was observed in African AIDS patients, compared with those with asymptomatic HIV-1 infection. This reduction in anti-p24 reactivity with more advanced clinical stage was less marked in African HIV-1 infection than in the UK. Correspondingly, p24 antigenaemia was more common in patients with AIDS from the UK than in African patients (65 versus 4%). Reductions in anti-gp120 reactivity were observed in African AIDS patients, compared with the asymptomatic group. However, median reactivity of anti-gp120 in UK patients remained unchanged in both asymptomatic and AIDS subjects. The differences in humoral response to p24 and gp120 between Africa and the UK are semi-quantitative rather than qualitative and could be explained by initial higher antibody response to HIV-1 in African subjects.

Infection and morbidity in patients with tuberculosis in Nairobi, Kenya.

OBJECTIVE: To examine the role of acute infection as a cause of morbidity in patients with tuberculosis. DESIGN: Cross-sectional documentation of predefined acute morbid events. SETTING: Infectious Diseases Hospital, Nairobi, Kenya. PATIENTS: Adults (> or = 15 years), inpatients and outpatients with a diagnosis of tuberculosis presenting with one or more of a series of clinical features. A new event was defined as one occurring at least 1 week after the initial event. INTERVENTIONS: Patients' treatment was modified depending on the results of laboratory investigations. MAIN OUTCOME MEASURES: There were 642 events from 398 patients, 235 HIV-positive patients had 438 events and 163 HIV-negative patients had 204 events (P < 0.0001). Forty-two out of the 235 (18%) HIV-positive patients were bacteraemic compared with nine out of the 163 (6%) HIV-negative patients (P = 0.0003). The most common isolates from blood were Salmonella typhimurium and Streptococcus pneumoniae. RESULTS: Faecal specimens were obtained more commonly from HIV-positive patients (P < 0.001), and often contained bacterial pathogens. CONCLUSIONS: Many of the causes of morbidity in patients with tuberculosis and HIV are not due to tuberculosis or antituberculous therapy, and will not be identified without microbiological investigation.

PIP: Tuberculosis (TB) is a common complication of HIV in Africa. A 1988-89 study further confirmed that considerable morbidity and mortality from acute bacterial infection occurred in HIV patients. It has also been found that anti-TB therapy seems to be as effective in HIV-positive as in HIV-negative TB patients. This paper reports on the level and nature of infectious morbidity suffered by HIV-positive patients receiving treatment for TB. The assessment is based upon a sample of inpatients and outpatients at the Infectious Diseases Hospital in Nairobi. Patients were aged 15 years and older, with a TB diagnosis presenting with 1 or more of a series of clinical features. 642 morbid events were seen in 398 patients: 235 HIV-positive patients had 438 event and 163 HIV-negative patients had 204 events. 18% of the HIV-positive patients versus 6% of the HIV-negative patients were bacteremic. Salmonella typhimurium and Streptococcus pneumoniae were most commonly isolated from sera, while fecal specimens were obtained more commonly from HIV-positive patients and often contained bacterial pathogens. The authors conclude that many causes of morbidity in patients with TB and HIV are not due to TB or anti-TB therapy and will not be identified without microbiological investigation. These results suggest that even with effective anti-TB chemotherapy HIV-positive patients will remain or become unwell.

Recent transmission of tuberculosis in a cohort of HIV-1-infected female sex workers in Nairobi, Kenya.

OBJECTIVES: To describe the epidemiological and clinical characteristics of HIV-related tuberculosis in a female cohort, and to investigate the relative importance of recently transmitted infection and reactivation in the pathogenesis of adult HIV-related tuberculosis. DESIGN: Members of an established cohort of female sex workers in Nairobi were enrolled in a prospective study. Women were followed up regularly and seen on demand when sick. METHODS: Between October 1989 and September 1992 we followed 587 HIV-infected and 132 HIV-seronegative women. Standard protocols were used to investigate common presentations. Cases of tuberculosis were identified clinically or by culture. All available Mycobacterium tuberculosis strains underwent DNA fingerprint analysis. RESULTS: Forty-nine incident and four recurrent episodes of tuberculosis were seen in HIV-infected women; no disease was seen in seronegative sex workers (P = 0.0003). The overall incidence rate of tuberculosis was 34.5 per 1000 person-years amongst HIV-infected participants. In purified protein derivative (PPD) skin test-positive women the rate was 66.7 per 1000 person-years versus 18.1 per 1000 person-years in PPD-negative women. Twenty incident cases (41%) were clinically compatible with primary disease. DNA fingerprint analysis of strains from 32 incident cases identified two clusters comprising two and nine patients; allowing for index cases, 10 patients (28%) may have had recently transmitted disease. Three out of 10 (30%) patients who were initially PPD skin test-negative became PPD-positive. Taken together, 26 incident cases (53%) may have been recently infected. DNA fingerprint analysis also identified two (50%) of the four recurrent tuberculosis episodes as reinfection. CONCLUSIONS: Substantial recent transmission of tuberculosis appears to be occurring in Nairobi amongst HIV-infected sex workers. It may be incorrect to assume in other regions of high tuberculosis transmission that active HIV-related tuberculosis usually represents reactivation of latent infection.

PIP: A 3-year (1989-92) prospective study of 587 HIV-positive and 132 HIV-negative commercial sex workers in Nairobi, Kenya, revealed substantial recent transmission of tuberculosis in the HIV-infected group. The cohort was enrolled at a community clinic that provides counseling, sexually transmitted disease services, and free condoms. In HIV-positive women, 49 incident and 4 recurrent episodes of tuberculosis were diagnosed during the study period; there were no tuberculosis cases among HIV-negative women. The overall incidence rate of tuberculosis was 34.5/1000 person-years among HIV-positive women. 20 incident cases (41%) met the clinical case definition of primary disease. DNA fingerprint analysis of strains from 32 incident cases suggested 10 women (28%) may have had recently transmitted disease. 3 of 10 women who were initially purified protein derivative (PPD) skin test-negative became PPD-positive. Clinical presentation, tuberculin skin testing, and strain clustering data all independently suggested that substantial Mycobacterium tuberculosis transmission was occurring in HIV-infected prostitutes during the study period. As many as 26 (53%) of the 49 patients with incident disease may have recently acquired tuberculosis and DNA fingerprint analysis identified 2 (50%) of the 4 recurrent tuberculosis episodes as reinfection. These findings challenge the assumption that tuberculosis in HIV-infected individuals represents reactivation of latent endogenous infection.

Extrapulmonary and disseminated tuberculosis in HIV-1-seropositive patients presenting to the acute medical services in Nairobi.

We studied 506 consecutive adult acute medical admissions to hospital in Nairobi; 95 (18.8%) were seropositive for HIV-1, and 43 new cases of active tuberculosis (TB) were identified. TB was clearly associated with HIV infection, occurring in 17.9% of seropositive patients compared with 6.3% of seronegatives [odds ratio (OR) 3.2; 95% confidence limits (CL) 1.6-6.5]. Extrapulmonary disease was more common in seropositive than seronegative TB patients (nine out of 17 versus five out of 26; OR 4.7; 95% CL 1.01-23.6); this accounted for most of the excess cases of TB seen in seropositive patients. Mycobacteraemia was demonstrated in two of eight seropositive TB patients but in none of 11 seronegative TB patients. No atypical mycobacteria were isolated. The World Health Organization (WHO) clinical case definition for African AIDS did not discriminate well between seropositive and seronegative TB cases. Five out of seven seropositive women with active tuberculosis had delivered children in the preceding 6 months and were lactating, compared with only one out of eight seronegative tuberculous women. An association between recent childbirth, HIV immunosuppression and the development of TB is suggested.

The risks and benefits of childhood bacille Calmette-Guérin immunization among adults with AIDS. International MAC study groups.

OBJECTIVE: To define the risks of disseminated bacille Calmette-Guérin (BCG) or disseminated Mycobacterium tuberculosis in adults with AIDS who were immunized with BCG in childhood. DESIGN: HIV-infected patients with CD4 < 200 x 10(6)/l were enrolled from five study sites (New Hampshire, Boston, Finland, Trinidad and Kenya). Prior BCG immunization was determined and blood cultures for mycobacteria were obtained at study entry and at 6 months. Acid-fast bacilli were identified as Mycobacterium tuberculosis complex (MTBC) using DNA probes. MTBC isolates were then typed by both IS6110 restriction fragment length polymorphism and polymerase chain reaction/restriction enzyme analysis. SETTING: Most patients in New Hampshire and Finland were outpatients; most patients in Trinidad were inpatients with terminal illness; and most patients in Kenya were outpatients, although 44 were inpatients with terminal illness. PARTICIPANTS: A total of 566 patients were enrolled, including 155 with childhood BCG immunization; 318 patients had a single study visit and culture, and 248 patients had two study visits and cultures. MAIN OUTCOME MEASURES: Isolation and identification of mycobacteria from blood cultures. RESULTS: Blood cultures were positive for MTBC in 21 patients; none were positive for M. bovis BCG, and 21 were M. tuberculosis-positive. In Trinidad, seven (87%) out of eight isolates of M. tuberculosis were indistinguishable by IS6110 typing; BCG immunization was associated with a decreased risk of bacteremic infection with M. tuberculosis (P = 0.05). CONCLUSIONS: The risk of disseminated BCG among adult AIDS patients with childhood BCG immunization is very low. Childhood BCG immunization is associated with protection against bacteremia with M. tuberculosis among adults with advanced AIDS in Trinidad.

The international epidemiology of disseminated Mycobacterium avium complex infection in AIDS. International MAC Study Group.

OBJECTIVE: To determine rates of disseminated Mycobacterium avium complex (MAC) infection among AIDS patients in developed and developing countries, and to determine whether different rates reflect differences in exposure or immunity, or both. DESIGN: Prospective cohort study. SETTING: University hospitals and outpatient AIDS programs. METHODS: HIV-infected subjects with CD4 counts < 200 x 10(6)/l were interviewed and had CD4 lymphocyte counts, blood cultures for mycobacteria (baseline and at 6 months), and skin tests with purified protein derivative (PPD) and M. avium sensitin. RESULTS: Among 566 study patients rates of disseminated MAC were 10.5-21.6% in New Hampshire, Boston and Finland compared to 2.4-2.6% in Trinidad and Kenya (P < 0.001). PPD skin test reactions > or = 5 mm were present in 20% of patients from Kenya compared to 1% at other sites (P < 0.001). Among patients from the United States and Finland, multiple logistic regression indicated that occupational exposure to soil and water was associated with a decreased risk of disseminated MAC, whereas the following were associated with an increased risk of disseminated MAC: low CD4 count, swimming in an indoor pool, history of bronchoscopy, regular consumption of raw or partially cooked fish/shellfish and treatment with granulocyte colony-stimulating factor. CONCLUSIONS: Rates of disseminated MAC in AIDS are higher in developed than developing countries and are due to both differences in exposure and differences in immunity. These data provide a rationale for prevention of MAC through both active immunization and reduction in exposure to the organism.

Nosocomial Legionnaires' disease--advances in diagnosis and typing.

The impact of new methodologies on the routine diagnosis of legionella pneumonia has been limited but the potential for advance is considerable. Antigen detection immunoassays have not yet reached the stage where they are used in routine practice. Monoclonal antibodies have been successfully used for direct fluorescence of bronchial aspirates. Nucleic acid hybridization techniques have yet to find a role in diagnosis. Serology remains the most commonly used method in the diagnosis of Legionnaires' disease. Methods of typing Legionella pneumophila include monoclonal antibodies and isoenzyme, plasmid and nucleic acid analysis. Biotyping methods have not been found to be of value. The use of monoclonal antibodies has permitted the comparison of clinical and environmental isolates and allowed the separation of serogroup 1 into subgroups of differing virulence. The subgroup of serogroup 1 called Pontiac is responsible for the majority of sporadic and epidemic legionella pneumonia in the UK. An internationally accepted panel of monoclonal antibodies is used to define these strains. The extent to which other subgroups of serogroup 1 and other serogroups of L. pneumophila cause disease appear to reflect their environmental prevalence.

Biochemical mis-identification of Brucella melitensis and subsequent laboratory-acquired infections.

Brucella species are mis-identified in the API 20NE system as Moraxella phenylpyruvica (profile number 1200004). Since some Brucella spp. grow readily in routine blood culture medium and may be isolated from patients without clinically obvious brucellosis, the risk of laboratory-acquired brucellosis exists. We describe two such cases.

Aspects of tuberculosis in Africa. 2. The value of microbiology in the management of tuberculosis in Nairobi, Kenya.

A group of African patients with tuberculosis were followed over the first month of treatment to assess the bactericidal response to 2 treatment regimens (streptomycin/thiacetazone/isoniazid and streptomycin/rifampicin/isoniazid/pyrazinamide). Patients also infected with human immunodeficiency virus (HIV) had lower pre-treatment counts of viable Mycobacterium tuberculosis and a greater proportion became culture-negative by 28 d. The response to therapy in HIV positive and HIV negative patients was similar. Because of the combination of these findings and the higher early mortality in patients with HIV, the causes of acute infection in patients with tuberculosis were studied. It was found that HIV positive patients were frequently bacteraemic and that the principal pathogen was Salmonella typhimurium, but recurrent pneumococcal bacteraemia was also seen.

PIP: Two studies of tuberculosis patients in Kenya are summarized in support of management programs that take into account concurrent infections, particularly human immunodeficiency virus (HIV). In the first study, HIV-negative patients had significantly higher (P = 0.019) pretreatment concentrations of Mycobacterium tuberculosis in the sputum. HIV-positive patients had less radiological evidence of disease and fewer cavities in the lungs. Responses to 2 chemotherapeutic regimens, streptomycin/thiacetazone/isoniazid/(STH) vs streptomycin/rifampicin/isoniazid/pyrazinamide (SRHZ), were the same in HIV-positive patients (55% culture-positive after 28 days) while 92% (STH) and 62% (SRHZ) of HIV-negative individuals were culture positive after 28 days. In view of these results, and the high morbidity and mortality of HIV-positive individuals, patients were surveyed in a second study for acute morbid events as defined by clinical signs. Blood and stool specimens were also cultured. Significantly more HIV-positive patients had 2 or more events (P 0.001) and were more likely to be bacteremic (P = 0.0003). The most common isolate was Salmonella typhimurium, but recurrent streptococcus pneumoniae was also seen. Fecal specimens from HIV-positive patients were more likely to be positive for bacterial pathogens (26% vs 7%, P = 0.08).

Toxoplasma antibodies in HIV-positive patients from Nairobi.

Sera from 94 patients infected with human immunodeficiency virus (HIV) 1, together with 86 controls, attending the Kenyatta National Hospital, Nairobi were examined for antibodies to Toxoplasma gondii using enzyme immunoassay and latex and dye tests. 54% had Toxoplasma-specific immunoglobulin G (IgG) by dye test. 22% of the HIV-positive group had IgG levels in excess of 180 units/ml (approximating to a dye test titre of 1:1300) compared to 1% of the HIV-negative group. There was no correlation between high levels of IgG and clinical stage of HIV disease or features indicative of active toxoplasmosis. It is proposed that the elevated serum IgG is a reflection of early Toxoplasma reactivation, not necessarily associated with disease.

PIP: Health workers took blood samples from 94 HIV positive patients (cases) and 86 HIV negative patients (controls) at the Kenyatta National Hospital in Nairobi, Kenya. Researchers compared the serological results of both groups to determine if any serological evidence of reactivation of latent infection existed and, if so, whether this reactivation could be related to acute toxoplasmosis. Laboratory personnel tested all serum with EIA and latex agglutination and dye tests to determine the presence of anti-Toxoplasma antibodies (Toxoplasma IgG). Both the EIA and latex test were more sensitive and specific in detecting Toxoplasma IgG than the dye test. The dye test revealed 54% of all patients had Toxoplasma IgG. Further 22% of the cases had IgG levels 180 units/ml whereas only 1% of controls had these levels. None of the patients exhibited any signs or symptoms of toxoplasmic encephalitis. Further no correlation between high Toxoplasma IgG titers and signs of central nervous system dysfunction or confusion occurred. Even though 35% of cases had considerable lymphadenopathy, it was not associated with Toxoplasma IgG levels. Moreover Toxoplasma IgG levels were not related to AIDS or death. The researchers concluded that high serum IgG levels were indicative of early Toxoplasma reactivation and necessarily associated with disease.

Brucellosis: imported and laboratory-acquired cases, and an overview of treatment trials.

Following the successful eradication of Brucella abortus infection in cattle, human brucellosis in England and Wales has become an uncommon imported disease. Culture of the organism presents a major laboratory hazard, and difficulties in identification may occur using a biochemical test-strip method. An overview of recent treatment trials of brucellosis indicates that regimens combining streptomycin and doxycycline are associated with a higher success rate (judged by the frequency of treatment failure and relapse following therapy) than combinations of rifampicin and doxycycline.

n-Alkyl fluorenyl phases in chromatography. II. Dynamic behavior and high-performance liquid chromatography applications.

The dynamic behavior of two n-hexyl fluorenyl phases (fluorene-6A [3a(Tn)(Qm)y], fluorene-6B [3b(Tn)(Qm)y]) and three n-decyl fluorenyl phases (fluorene-10A [4a(Tn)(Qm)y], fluorene-10B [4b(Tn)(Qm)y], and fluorene-10C [4c(M1)(Qm)y]) is investigated by solid-state nuclear magnetic resonance (NMR) spectroscopy using the dipolar filter technique with both 13C and 1H detection. These results are compared with those from other dynamic measurements, like the relaxation times in the rotating frame (T1pH) and the variation of the contact time (T(CH)). Additionally, another type of a fluorenyl phase [5a(Tn)(Qm)y], which has an aromatic moiety connected to the silica gel by amido couplings, was also investigated by the dipolar filter method. The solid-state NMR dynamic measurements indicate an increased mobility of the n-alkyl fluorenyl phases compared to the amido coupled fluorenyl phase. The lower the ligand density of the studied n-alkyl fluorenyl phases, the higher their mobility. The separation behavior of the respective phases in high-performance liquid chromatography was investigated with samples containing polycyclic aromatic hydrocarbons and nitro explosives. Depending on the amount of the chemically bound aromatic moiety and the length of their n-alkyl spacer groups, pi-pi interactions with the solute molecules are involved in the separation process and cause it to proceed at a different rate. Therefore, n-alkyl fluorenyl phases can be classified as mixed-mode phases.

Peroxisome proliferator-activated receptor (PPAR) alpha-regulated growth responses and their importance to hepatocarcinogenesis.

Peroxisome proliferators (PPs) are a class of non-genotoxic rodent hepatocarcinogens that act by perturbing liver growth regulation. We have demonstrated previously that PPs suppress both spontaneous rat hepatocyte apoptosis and that induced by exogenous stimuli such as transforming growth factor-beta1 (TGF beta1). More recently, we have demonstrated that PPs can suppress apoptosis induced by more diverse stimuli such as DNA damage or ligation of Fas, a receptor related to the tumour necrosis factor alpha (TNF alpha) family of cell surface receptors. PPs transcriptionally activate the peroxisome proliferator activated receptor-alpha, PPAR alpha, a member of the nuclear hormone receptor superfamily. We investigated whether activation of PPAR alpha mediates the suppression of rat hepatocyte apoptosis induced by PPs. We isolated a naturally occurring variant form of PPAR alpha (hPPAR alpha-6/29) from human liver by PCR cloning. hPPAR alpha-6/29 shared the ability of mPPAR alpha to bind to DNA but, unlike mPPAR alpha, could not be activated by PPs. Furthermore, hPPAR alpha-6/29 could act as a dominant negative regulator of PPAR-mediated gene transcription. When introduced into primary rat liver cell cultures by transient transfection, hPPAR alpha-6/29 prevented the suppression of hepatocyte apoptosis by the PP nafenopin, but not that seen in response to phenobarbitone (PB), a non-genotoxic carcinogen whose action does not involve PPAR alpha. The suppression of hepatocyte apoptosis was abrogated completely even though only 30% of hepatocytes were transfected, suggesting the involvement of a soluble factor. Recent data have suggested that TNF alpha, perhaps released by liver Kupffer cells in response to PPs, may play a key role in mediating the effects of PPs on hepatocyte growth regulation.

Solid state NMR and extraction studies on "phenyl"-bonded stationary phases used for solid phase extraction.

The solid phase extraction (SPE) and elution of [14C]-propranolol from aqueous buffer has been studied for a range of phenyl-bonded SPE materials. Differences were noted in the recovery of the analyte using methanol-water eluents depending upon the manufacturer and whether or not phase had been endcapped. Efficient recoveries of [14C]-propranolol were only achieved when triethylamine was added to the eluting solvent as a competing base. Solid state cross polarisation/magic angle spinning (CP/MAS) NMR spectroscopy was used to characterise the phases further, which revealed differences in endcapping between materials as well as differences in the type and extent of cross-linking.

Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis.

BACKGROUND: Since the sterilising activity of new antituberculosis drugs is difficult to assess by conventional phase III studies, surrogate methods related to eventual relapse rates are required. METHODS: A suitable method is suggested by a retrospective analysis of viable counts of Mycobacterium tuberculosis in 12-hr sputum collections from 122 newly diagnosed patients with pulmonary tuberculosis in Nairobi, done pretreatment and at 2, 7, 14 and 28 days. Treatment was with isoniazid and streptomycin, supplemented with either thiacetazone (SHT) or rifampicin + pyrazinamide (SHRZ). RESULTS: During days 0-2, a large kill due to isoniazid occurred, unrelated to treatment or HIV status; thereafter it decreased exponentially. SHRZ appeared to have greater sterilising activity than SHT during days 2-7 (p = 0.044), due to rifampicin, and during days 14-28, probably due mainly to pyrazinamide. The greatest discrimination between SHRZ and SHT treatments was found between regression estimates of kill over days 2-28 (p = 0.0005) in patients who remained positive up to 28 days with homogeneous kill rates. No associations were found between regression estimates and the age, sex, and extent of disease or cavitation. An increased kill in HIV seropositive patients, unrelated to the treatment effect, was evident during days 2-28 (p = 0.007), mainly during days 2-7. CONCLUSIONS: Surrogate marker studies should either be in small groups treated with monotherapy during days 2 to about 7 or as add-ons or replacements in isoniazid-containing standard regimens from days 2 to 28 in large groups.

Local street speed management in Australia--is it "traffic calming"?

A small sample of recent developments in local speed management and safety in Australia is outlined to illustrate conclusions about practice and assessment. This experience seems to support the effectiveness of devices in lowering speeds and reducing accidents, but there is still generally a lack of adequate monitoring and evaluation. Speeds in new residential areas require attention in the planning and design stages; some current fads in neighbourhood planning threaten to perpetuate old traffic problems. The current use of the term traffic calming to mean reduction of car travel demand rather than restraint on driver behaviour and route choice is noted. It is suggested that citywide suppression of traffic goes beyond "traffic calming" as it is commonly understood, into the realm of travel demand management and cultural change.