Occupational asthma caused by cellulase and lipase in the detergent industry.

Three employees from two different detergent companies were investigated for occupational asthma, using skin prick tests, serum specific IgE, and specific bronchial challenge. Two were challenged with lipase and one with cellulase. All three cases had immunological evidence of sensitisation to the detergent enzymes with which they worked. Bronchial challenge in each provoked a reproducible dual asthmatic response, which reproduced their work related symptoms. These are the first reported cases of occupational asthma attributable to cellulase and lipase in the detergent industry. Four of the most common enzymes used in this industry have now been reported to cause occupational asthma; continued vigilance and caution are needed when working with these or other enzymes.

Reference intervals for procalcitonin and C-reactive protein after major abdominal surgery.

Procalcitonin (PCT). a new marker proposed as a diagnostic tool for bacterial infections, triggers a systemic-inflammatory reaction in the body (sepsis, septic shock) and has potential use in a wide range of patient settings. To interpret the results from PCT measurements, we depend on reference intervals established from relevant populations. PCT and C-reactive protein (CRP) concentrations were analysed in 47 patients with a normal postoperative course after major abdominal surgery. The mean concentration of PCT declines from the first day and reaches half its initial values on the second day after the operation. whereas the mean concentration of CRP increases in the first 48 h and reaches half its maximum value on the fifth day after the operation. We present a continuous reference interval for plasma PCT and CRP concentrations in the first week following major abdominal surgery. For PCT we also present a graphic display of expected mean and expected upper reference limits predicted from the value measured on the first postoperative day.

A randomised study of prophylactic G-CSF following MRC UKALL XI intensification regimen in childhood ALL and T-NHL.

BACKGROUND: Despite the current widespread use of prophylactic G-CSF in children with solid tumours and leukaemia, its effectiveness has not been clearly demonstrated. This randomised study evaluates the role of G-CSF given after a 5-day intensification block in children with acute lymphoblastic leukaemia (ALL). PROCEDURE: Forty-six children with ALL or T-Cell non-Hodgkins lymphoma (NHL) treated on MRC ALL 97, UKALL XI or UKCCSG 9504 NHL protocols were randomised to receive granulocyte colony-stimulating factor following either the first or the second block of intensive chemotherapy in a cross-over study to determine if the prophylactic administration of G-CSF could reduce the rate of readmission to hospital for management of febrile neutropenia. RESULTS: There was a statistically significant difference in the rate of hospital admission in the group receiving prophylaxis, with 34 of 46 being admitted, compared to 42 of 46 patients in the control arm (74 vs. 91%; P=0.0386). There were no differences found in duration of hospital admission, haematological toxicity, neutrophil recovery or duration of supportive care between the two groups. There was no demonstrable cost benefit derived from the prophylactic administration of G-CSF. CONCLUSIONS: This study shows that the prophylactic administration of G-CSF following intensification chemotherapy for childhood ALL and T-NHL produces a significant reduction in the rate of readmission to hospital for the management of febrile neutropenia.

Crete: does farming explain urban and rural differences in atopy?

BACKGROUND: Urban-rural differences in the prevalence of atopy and associated allergic diseases have been reported in several non-European countries. Within Europe, where such variations are less striking, a farm childhood has been postulated to be protective. OBJECTIVE: We aimed to compare the prevalence of atopy in urban and rural children living in Crete and to examine the role of early exposure to a farming environment in explaining any measured differences. METHODS: A cross-sectional survey of children attending secondary schools in Iraklion, the capital city, and five villages 100 km to the south. Atopy was determined by the responses to skin prick tests with seven common aeroallergens. RESULTS: Nine-hundred and ninety-seven children participated in the survey. 19.6% of those living in Iraklion, but only 9.6% of those from the villages, had a positive response to one or more skin prick tests. Among urban children there were significant gradients in the prevalence of atopy across several categories of animal contact and consumption of farm (unpasteurized) milk products--before the age of 5 years. These differences, however, were not apparent among the rural children.

Amlodipine gynaecomastia.

We report only the second published confirmed case of gynaecomastia caused by amlodipine (a dihydropyridine calcium channel blocker). Gynaecomastia developed in a 70-year-old male within 3 months of starting amlodipine, and symptoms resolved within 3 weeks of drug withdrawal suggesting a strong relationship between amlodipine and gynaecomastia in this patient. Recent research has suggested possible interesting novel mechanisms for amlodipine gynaecomastia, which are discussed.

An outbreak of asthma in a modern detergent factory.

The striking decrease in the occurrence of protease-induced occupational asthma in the detergent Industry has been attributed to enzyme encapsulation. We report an outbreak of asthma, at least equal in size to those reported in the 1960s, in a modem European factory which has exclusively used encapsulated enzymes. A survey revealed that enzyme sensitisation and work-related respiratory symptoms were positively correlated with airborne enzyme exposure. We suggest that encapsulation alone is insufficient to prevent enzyme-Induced allergy and asthma.

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV(1)) were recorded and histamine provocative concentration causing a 20% fall in FEV(1) (PC(20)) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.

Laboratory exposure to cocaine cues does not increase cocaine use by outpatient subjects.

Sixty-nine cocaine-dependent outpatients were exposed to cocaine-related stimuli and to non-drug events on separate days. Cocaine cue sessions were always followed by a meeting with a trained clinician designed to eliminate any craving that remained following cue presentations. Urine samples were collected before each laboratory session and 1 to 3 days later. Neither rates of cocaine use nor average urine metabolite values differed following the two sessions. Nearly 90% of subjects had the same urine test result both before and after the cocaine cue session. Thus, laboratory presentation of cocaine cues to outpatient subjects did not increase their risk of subsequent drug-taking. These results suggest that with proper clinical protections, cue exposure can be used as a treatment outcome measure and a behavioral intervention in outpatient settings without increasing the risk of drug use.

Production of digoxigenin-labelled RNA probes and the detection of cytokine mRNA in rat spleen and brain by in situ hybridization.

Non-radioactive in situ hybridization is a sensitive method for determining the site of production for secretory molecules such as cytokines. We report here on the central and peripheral induction of proinflammatory cytokines by endotoxin, and outline procedures for the generation and application of rat-specific digoxigenin (Dig)-labelled RNA probes for the localization of mRNA by in situ hybridization. Rats were injected either intravenously (i.v.) or intracerebroventricularly (i.c.v.) with vehicle or lipopolysaccharide (LPS) and sacrificed at various time intervals post-injection. Rats were then perfused with 4% paraformaldehyde and the spleens and brains were removed and cryoprotected in 30% sucrose. Dig-labelled, rat-specific, antisense and sense RNA probes were generated by in vitro transcription from PCR-derived templates. Positive staining with all the antisense probes was cytoplasmic, whereas the sense probes showed no staining. Numerous tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1beta) mRNA positive cells were observed in the marginal zone and in the red pulp of the spleen after iv LPS injections, whereas sections from saline-treated animals showed minimal cytokine mRNA expression. Cells positive for TNF-alpha and IL-1beta mRNA were detectable in the brain after i.c.v. injections of LPS, but not after icv injection of vehicle. An antisense probe for c-fos was utilized in these studies as a positive control for our procedure due to its anatomically specific expression in the rat brain after LPS. In conclusion we have demonstrated that in situ hybridization with Dig-labelled RNA probes is an efficient, sensitive and reliable tool to localize cytokine mRNA production in rat tissue.

CD44 variant expression and estrogen receptor status in breast cancer.

To understand the relationship between CD44 gene expression and an established variable associated with aggressive behaviour in human breast cancer, we have studied a panel of 6 breast cell lines and 40 breast tumors selected primarily on the basis of estrogen receptor (ER) status. CD44 (standard form) mRNA was assessed by semi-quantitative RT-PCR, and CD44 variants incorporating exon v7 or v10 were studied by RT-PCR and Southern blot. While CD44 expression was not influenced by estrogen in ER+ve MCF-7 cells. CD44s expression was slightly higher (up to 2 fold) in ER-ve cells but there was a marked decrease in the range of CD44 variants incorporating exons v7 or v10. In microdissected tumors, the levels of CD44s showed no correlation with ER status but the pattern of expression of larger forms of CD44 incorporating variant exons v7 and v10 was significantly different (p = 0.005 and p = 0.015, respectively) between ER+ve and ER-ve tumors, reflecting the pattern seen in the cell lines. These findings suggest that the profile of CD44 expression in breast cancer may reflect cellular differentiation as indicated by the ER phenotype. The influence of these differences in CD44 expression on the increased metastatic potential of ER negative breast cancer remains to be determined.

Biphasic time-course of serum concentrations of clomipramine and desmethylclomipramine after a near-fatal overdose.

A 27-y-old male was admitted deeply comatosed 5-6 h after taking approximately 15 g clomipramine. The prominent feature of the case was a biphasic course of clomipramine and desmethylclomipramine serum concentrations, possibly caused by delayed drug absorption. Clinically, 2 serious episodes requiring mechanical ventilation and aggressive pressor agent infusions occurred as the serum concentrations declined. However, the severe adult respiratory distress syndrome--related inflammatory process that required 4 w of intensive care may also be an explanation, although blood cultures were negative and neither liver nor renal functions were severely compromised.

Cue reactivity and cue reactivity interventions in drug dependence.

Despite a venerable history dating back to Pavlov and countless testimonials from patients such as those in the opening paragraphs of this chapter, there is much that remains to be learned about drug signals and, particularly, about ways of reducing their adverse effects on human drug users. There is a substantial amount of data showing increased craving and signs of physiological arousal to drug-related versus neutral cues in drug users for both drug classes reviewed here. Additional controlled studies will be useful in refining which responses among those studied are, in fact, conditioned in origin and therefore can be subjected reasonably to learning-based interventions. Most attempts to modify cue responsivity for clinical benefit have met with only modest success, and there is ample room for creative, but controlled, treatment-outcome studies. In recent years, several other groups have joined in the effort to understand drug-related cue reactivity, extending the research area to alcohol and nicotine (Monti et al. 1987; Niaura et al. 1988, 1989; Cooney et al. 1984; Hodgson and Rankin 1982; Drummond 1990; Laberg 1990). The interested reader is referred to several additional reviews of cue reactivity and cue exposure research related to alcohol and nicotine (Niaura 1988; Drummond 1990; Laberg 1990), opiates (Powell 1990), opiates and cocaine (Childress et al. 1988b; O'Brien et al. 1990), and all the preceding areas (Rohsenow et al. 1991).

Pharmacokinetics of midazolam and alfentanil in outpatient general anesthesia. A study with concomitant thiopentone, flumazenil or placebo administration.

The pharmacokinetics of alfentanil, midazolam and thiopentone used for induction of short general anaesthesia were studied in 55 gynaecological outpatients. All the patients received midazolam as premedication. The patients received intravenous anaesthesia with alfentanil and either thiopentone or midazolam, supplemented with either nitrous oxide or air in oxygen ventilation, reversed by the end of anaesthesia with either placebo or flumazenil. Blood sampling for serum concentration measurements of midazolam, alfentanil and thiopentone was performed regularly for 7 h. The following mean pharmacokinetic parameters (mean +/- s.e. mean) were calculated for midazolam and alfentanil, respectively: elimination half-life 3.9 +/- 0.3 h and 1.2 +/- 0.05 h, apparent volume of distribution 107 +/- 61 and 31 +/- 1.5 l, total body clearance 20 +/- 0.7 l/h and 18 +/- 0.8 l/h. No influence of flumazenil on the kinetics of midazolam and no influence of thiopentone, midazolam, flumazenil or nitrous oxide on the kinetics of alfentanil was found. The serum levels of thiopentone were below the detection limit of the assay after 60 min, which made an evaluation of pharmacokinetic parameters impossible. Significant positive correlations were found in the individual patient between midazolam and alfentanil for all pharmacokinetic variables evaluated. For midazolam, an increase in the elimination half-life and the apparent volume of distribution was positively correlated to an increase of body-weight. For alfentanil, a decrease in the total body clearance and an increase in the elimination half-life were positively correlated to an increase of age. A prolonged elimination half-life of alfentanil was positively correlated to use of alcohol. High serum levels of thiopentone were positively correlated to increasing age of the patients.

Total intravenous anaesthesia with midazolam and flumazenil in outpatient clinics. A comparison with isoflurane or thiopentone.

Total intravenous anaesthesia with midazolam and alfentanil, reversed with the benzodiazepine antagonist flumazenil, was studied in patients admitted for outpatient gynaecological dilatation and curettage. One hundred patients were randomly allocated to four groups with different anaesthetic techniques: I: alfentanil and thiopentone induction, 66% N2O maintenance; II: alfentanil and midazolam sedation prior to isoflurane and N2O induction and maintenance; III: midazolam and alfentanil induction; oxygen/air, placebo reversal; IV: midazolam and alfentanil induction, oxygen/air, flumazenil reversal. All methods of anaesthesia proved satisfactory with no serious side-effects or complications. Induction was faster in Group I (26 s) compared with Group III and IV (37-38 s) and Group I (62 s). Respiration was less depressed in Group II compared with the other groups. Recovery function was better in Group IV during the first 30 postoperative min and worse in Group III during the first 120 postoperative min compared with the other groups. Reduced performances in P-deletion and 4-choice reaction-time tests in the midazolam patients were not reversed by 0.5 mg flumazenil, suggesting that flumazenil did not antagonize all benzodiazepine effects in our patients. Postoperative amnesia was most pronounced in Group III. There was no significant difference in patient function 7 h postoperatively, at home in the evening or during the next days. We conclude that total intravenous anaesthesia with alfentanil and midazolam with flumazenil reversal is a promising technique for short outpatient anaesthetic procedures.