Utility of single versus multiple breath washout in adult asthma.

Nitrogen multiple breath washout (N2 MBW) is a sensitive method to identify peripheral airway involvement in asthma, but is a time-consuming test. The N2 vital capacity single breath (VC SBW) test offers greater time efficiency, but concordance with N2 MBW is poorly understood. The prevalence of peripheral airway abnormality was determined by N2 MBW and N2 SBW tests in 194 asthmatic subjects aged 18-1 years. N2 MBW data were related to findings in 400 healthy controls, aged 17-71 years, while N2 SBW data were compared to findings in 224 healthy controls, aged 15-65 years, to derive equipment-specific reference values. Amongst asthmatic subjects, relationships between N2 SBW and N2 MBW outcomes were studied. N2 SBW relationship with clinical history, spirometry, blood eosinophils and fraction exhaled nitric oxide (FENO) data was also explored. The prevalence of peripheral airway involvement (i.e. abnormal ventilation distribution) determined by N2 SBW-derived phase III slope (N2 SIII ) was 24·7%, compared to 44% determined by N2 MBW-derived lung clearance index (LCI) (P<0·001). Predictors of abnormal N2 SIII were older age, smoking history and lower FEV1. N2 SBW offers lower sensitivity than N2 MBW to detect small airway dysfunction in adult asthma, but may be a marker of more severe disease.

Clinical characteristics of adult asthma associated with small airway dysfunction.

Suboptimal asthma control is common despite modern asthma therapy. The degree of peripheral airway involvement remains unclear and poor medication delivery to these regions might be a contributing reason for this failure in obtaining adequate symptom control. A cohort of 196 adults (median (range) age 44 (18-61) years, 109 females, 54 ex-smokers, six current smokers) with physician-diagnosed asthma were recruited from primary care. Subjects were characterized clinically by interviews, questionnaires, skin prick tests (SPT) and blood eosinophil counts. Lung function was assessed by spirometry, impulse oscillometry (IOS) and nitrogen multiple breath washout (N2 MBW). IOS assessed peripheral airway resistance (FDR, frequency dependence of resistance). N2 MBW assessed global ventilation inhomogeneity (LCI, lung clearance index), specific indices of peripheral airway function (Scond × VT and Sacin × VT; VT, tidal volume), and inter-regional inhomogeneity (specific ventilation ratio). Never-smoking healthy cohorts of 158 and 400 adult subjects provided local reference values for IOS and N2 MBW variables, respectively. Peripheral airway dysfunction was detected in 31% (FDR or specific ventilation ratio) to 47% (Scond x VT) of subjects. Risk factors for peripheral airway dysfunction were identified. Among subjects with low FEV1 and either positive smoking history and/or blood eosinophilia (>4.0%), 63% had abnormality across all peripheral airway outcomes, whilst only one subject was completely normal. Abnormal peripheral airway function was present in a large proportion of adult asthmatics at baseline. Reduced FEV1, a positive smoking history, and/or blood eosinophilia identified "a small airway asthma subtype" that might benefit from peripheral airway targeted therapy.

Blocking antibodies in blood from patients with recurrent spontaneous abortion in relation to pregnancy outcome and intravenous immunoglobulin treatment.

PROBLEM: To study whether the occurrence of mixed lymphocyte culture (MLC) blocking antibodies is associated with pregnancy outcome in women with unexplained recurrent spontaneous abortion (RSA) and the in vivo effect of intravenous immunoglobulin (IVIG) treatment on MLC blocking effect. METHOD OF STUDY: Blood samples from 41 RSA patients were obtained before and after pregnancy, and blocking antibodies were estimated by one-way MLC assay. The patients received IVIG or placebo (saline) during pregnancy. Additionally, prepregnancy blood samples from 31 RSA women and 10 controls were obtained. RESULTS: We found no correlation between blocking antibodies before pregnancy and the pregnancy outcome. The occurrence of blocking antibodies was not affected by pregnancy or IVIG treatment. CONCLUSIONS: Blocking antibodies have no predictive value for the pregnancy outcome in RSA patients, and their production seems not to be affected by IVIG.

Knowledge of and attitudes towards infertility held by members of two county councils in Sweden.

BACKGROUND: To investigate Swedish county council members knowledge of the laws regulating infertility treatment, their understanding of the suggestions put forward in the report 'Priorities in Health Care' and their attitudes towards infertility. METHODS: All members (n=182) of the 1998 county councils of Linköping and Jönköping were asked to participate in the study. In total, 153 answered the questionnaire. RESULTS: Different age groups did not show different levels of knowledge. Similarly, there was no significant difference between men and women concerning their knowledge of infertility laws. Furthermore, those committee members who were very positive towards infertility treatment did not have any better knowledge of such treatment than those who were less positive. The men and women who themselves had previously had or were dealing with infertility problems at the time of the survey (12 per cent) displayed the same level of knowledge as the other council members. They also expressed similar attitudes. The members showed very little familiarity with the priority groups suggested in the report from the Health Care Priority Committee. For example, only 18 per cent knew that this committee in priority group III placed infertility treatment and investigation. 31.3 per cent answered that infertility was placed in group V, a group that does not exist. The majority stated that they had a positive attitude towards the treatment of infertility. This is indicated, for example, by their rejection of the statement 'it's [infertility is] a luxury problem'. CONCLUSIONS: The relative lack of knowledge of Swedish law and of the report from the Health Care Priority Committee might lead to a lower level of commitment to dealing with the problems that infertile couples face than if the members were better informed. In other words, this lack of knowledge might influence the decisions of the county council members.

Prevention of recurrent spontaneous abortion by intravenous immunoglobulin: a double-blind placebo-controlled study.

The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin (IVIG) in the prevention of recurrent spontaneous abortion (RSA). In a double-blind, randomized, placebo-controlled study, 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy. The birth of a child was considered a successful outcome. The overall success rate was 77% in the IVIG group compared with 79% in the placebo group. For women with primary RSA the success rates were 82 (IVIG) and 89% (placebo), and for women with secondary RSA the rates were 73 (IVIG) and 70% (placebo). We found no statistically significant difference in treatment results between IVIG and placebo.

A comparison of 5-minute povidone-iodine scrub and 1-minute povidone-iodine scrub followed by alcohol foam.

The purpose of this study was to determine if a 1-minute scrub with povidone-iodine followed by alcohol foam is as effective as a 5-minute scrub with povidone-iodine in reducing skin bacterial counts. A 1-minute scrub with povidone-iodine followed by alcohol foam and a 5-minute scrub with povidone-iodine was done. In the first study, cultures were obtained after 1 hour, and in the second study, cultures were obtained after 2 hours. Cultures were obtained by imprinting the first, second, and third fingers on nutrient agar plates. Bacterial counts were then obtained at 24 and 48 hours. The study involved two groups of 12 participants and a total of 37 patients over a period of 5 months. The results show that there was no significant difference between the number of colonies cultured for the 1-minute scrub compared with the 5-minute scrub for either the 1-hour or the 2-hour study. In fact, the total number of bacterial colonies was less after the 1-minute scrub with alcohol foam than after the standard 5-minute scrub in both the 1-hour group (10 vs. 18) and the 2-hour group (18 vs. 44).

Pleural cytologies in lung cancer without pleural effusions.

BACKGROUND: Malignant pleural effusions significantly increase the stage of lung cancer with attendant worsening of prognosis. There is a paucity of literature evaluating malignant pleural lavage cytology in patients without pleural effusions. We propose to determine the incidence of malignant pleural cytologies in patients without pleural effusions who undergo curative resection for lung cancer and to identify any predictive risk factors for positive cytology. METHODS: Seventy-eight patients underwent curative resection for lung cancer. Lavage was performed before lung manipulation and after resection and cytologically evaluated. RESULTS: Twelve pneumonectomies, 64 lobectomies, and 2 wedge resections were performed on 40 men and 38 women with an average age of 65.7 years. Fourteen percent had positive lavage cytology before lung resection with an 11% (6 of 53) incidence in stage I. A significant correlation to adenocarcinoma compared with squamous cell was found (p = 0.03) but not to stage, T or N status, grade, pleural invasion, or preoperative transthoracic needle biopsy. CONCLUSIONS: The incidence of positive pleural cytology in otherwise stage I patients is disconcertingly high. Positive cytology may be a prognosticator of a more aggressive tumor biology.

Summer mastitis experimentally induced by Hydrotaea irritans exposed to bacteria.

Summer mastitis is an acute suppurative bacterial infection of the udder in heifers and dry cows. To ascertain the possible role of flies in the transmission of the disease, experimental exposures of recipient heifers to Hydrotaea irritans previously exposed to bacteria were carried out. Flies were allowed to feed on secretions from clinical cases of summer mastitis. The pathogens present were the bacteria Staphylococcus aureus, Streptococcus dysgalactiae, Actinomyces pyogenes, Stuart-Schwan cocci, Peptococcus indolicus, Fusobacterium necrophorum and Bacterioides species. The teats of eight heifers were exposed to flies with verified pathogen content. Two teats of each animal were deliberately damaged before fly exposure. One teat was cut, another pricked with insect needles to mimic insect bites. Two of the heifers developed summer mastitis in the quarters where teats had been cut. The bacterial species isolated from these quarters corresponded to those that had previously been fed to the flies. For the first time, it is now demonstrated that H.irritans is capable of transmitting summer mastitis pathogens and so causing summer mastitis in recipient heifers. Lesions on the teat orifice may be a predisposing factor in the development of the disease.

Occult inguinal hernia, a cause of rapid onset of penile and scrotal edema in patients on chronic peritoneal dialysis.

From 1976 to 1993 we inserted 160 chronic peritoneal dialysis catheters for renal failure patients. Three of these patients developed sudden onset of penile and scrotal edema after the catheter had been in place for several months. The first patient was diagnosed by instilling technetium sulfur colloid in the peritoneal cavity, which showed the radioisotope flowing via the right inguinal canal. He was operated on and the processus vaginalis was tied off and the scrotal and penile edema resolved. Subsequently, two more patients were seen with similar problems and had their inguinal canals explored and the processus vaginalis in one and the hernia sac in the other were found and tied off, which resulted in resolution of the problem. This is an uncommon complication, reported to occur in 3 to 4% of patients.

The relationship of radon to gastrointestinal malignancies.

Radon has known and well-studied carcinogenic effects on pulmonary epithelium. The gastrointestinal tract has potential for radon exposure by swallowed air and/or pulmonary secretions or contaminated drinking water. However, the relationship between radon and gastrointestinal malignancies is poorly documented. Therefore, the purpose of this study was to investigate a potential relationship between radon levels and gastrointestinal malignancies within the Commonwealth of Pennsylvania. In a retrospective analysis, the radon levels as reported by the Department of Environmental Resources for each county in Pennsylvania were compared to the incidence and mortality of gastrointestinal cancer in Pennsylvania by county as reported by the Pennsylvania Tumor Registry from 1985 to 1989. The incidence and mortality of stomach, esophagus, colon, pancreas, and rectal cancer was reported for male, female, and total county population and compared to radon levels for that county. Using the NCSS computer package with P value set at 0.05, a positive correlation was found between radon levels and the incidence of stomach cancer in females, and the mortality of stomach cancer for male, female, and total population. This study suggests a relationship between radon levels and gastric cancer mortality. Further investigation into the role of radon carcinogenesis may be warranted.

Sperm chromatin stability and zinc binding properties in semen from men in barren unions.

Sperm chromatin stability and zinc binding properties were studied in semen samples from 115 men living in barren unions. Of these men, 26% had a high proportion of swelling sperm, i.e. less than 80% sperm with stable chromatin after exposure to the detergent sodium dodecyl sulphate. From 2-67% of seminal zinc was bound to high molecular weight ligands of vesicular origin (HMW). This shows that, among infertile men, liquefied seminal plasma has huge variations in zinc chelating properties. The relationship between prostatic palpatory status, the proportion of abnormal sperm, the percentage zinc bound to HMW (HMW-Zn), the time between ejaculation and analysis and chromatin stability were studied. Samples with low chromatin stability were found more frequently in men with low HMW-Zn levels in semen. The proportion of stable sperm decreased in samples with prolonged exposure to seminal plasma. Neither the proportion of stable sperm heads nor the percentage zinc bound to HMW could be used to predict the future chances of the infertile men fathering children when studied 15-180 min after ejaculation. To differentiate between initial zinc-dependent stability and superstability developed in seminal plasma, other more sensitive methods must be developed.

Ejaculatory sequence in men with low sperm chromatin-zinc.

The composition of seminal plasma in the sperm-rich split ejaculate fraction was studied in a group of men with a low zinc content in their sperm chromatin, to evaluate the availability of zinc at ejaculation. Men with low-chromatin zinc had, in the sperm-rich split-ejaculate fraction, high amounts of seminal-vesicular fluid, a low zinc:fructose molar ratio, and a high percentage of zinc bound to high molecular weight ligands of seminal vesicular origin (HMW-Zn). This indicates premature admixture of vesicular fluid at ejaculation. It is suggested that the zinc:fructose molar ratio and HMW-Zn in the sperm-rich fractions could be used as a measure of the availability of zinc in seminal plasma.

Seminal fluid from men with agenesis of the Wolffian ducts: zinc-binding properties and effects on sperm chromatin stability.

Zinc-binding properties were studied in 'prostatic fluid', i.e. in seminal plasma from patients with agenesis of the Wolffian ducts, and in split-ejaculate fractions dominated by seminal vesicular fluid. The effect of seminal fluid, with different zinc-binding properties, on the stability of zinc-dependent sperm chromatin was assessed by exposing sperm to 1% sodium dodecyl sulphate (SDS) for 60 min. Citrate was the only zinc ligand in 'prostatic fluid', as revealed by gel chromatography. Zinc in this fluid enhanced the stability of sperm chromatin. In contrast, the stability of sperm chromatin was decreased in seminal plasma dominated by vesicular fluid. These results are in accordance with the concept that prostatic fluid ensures the appropriate zinc content and stability of sperm chromatin, whereas abundance of vesicular fluid may jeopardize chromatin stability by reducing chromatin zinc content.

Zinc in sperm chromatin and chromatin stability in fertile men and men in barren unions.

The stability and the content of zinc of the chromatin were studied in spermatozoa from ten men with unexplained infertility, and in spermatozoa from five fertile donors. A positive relation was found between zinc in sperm nuclei (X-ray microanalysis) and the resistance of the chromatin to decondense in sodium dodecylsulfate (SDS). The infertile men had lower degree of sperm chromatin stability and lower sperm zinc content than the fertile donors. A subgroup of the infertile men, which all had minor clinical signs of prostatic inflammatory reaction, had the lowest content of zinc in the chromatin and the lowest degree of chromatin stability. A low content of nuclear zinc would impair the structural stability of the chromatin and thereby increase the vulnerability of the male genome. This mechanism may be one explanation for the reduced fertility of the men with minor inflammation of the prostate.

Sperm nuclear zinc, chromatin stability, and male fertility.

Zinc excreted from the human prostate secures a high content of zinc in the sperm nucleus and contributes to the stability of the quaternary structure of the chromatin. After ejaculation, in vitro, a second type of stability, most probably involving disulfide-bridge crosslinks, supersedes the zinc-dependent stability. Normally, the nucleus of the ejaculated spermatozoon remains stable, i.e., it does not decondense when exposed to a detergent (e.g., sodium dodecyl sulfate - SDS), whereas a spermatozoon which has been exposed to a zinc-chelating medium becomes destabilized and decondenses in SDS. Spontaneous decondensation in SDS, i.e., without prior treatment with zinc-chelators, occurs among many spermatozoa from some infertile men, especially men with impaired secretory function of the prostate. This indicates that spontaneously decondensing spermatozoa have an inadequate content of zinc at ejaculation. Here, zinc in the sperm nucleus and chromatin stability was studied in semen samples from a group of men living in marriages with hitherto unexplained cause for infertility, and a group of fertile donors, who participated in an insemination program. Sperm nuclear zinc was studied with X-ray microanalysis and chromatin stability was assessed as percentage spermatozoa with stable sperm heads after exposure to SDS. Fertile donors had higher content of zinc in the sperm nuclei and had also higher proportions spermatozoa with a stabilized chromatin, than had the men living in infertile marriages.(ABSTRACT TRUNCATED AT 250 WORDS)

The human sperm nucleus takes up zinc at ejaculation.

Ejaculated and vasal sperm were obtained from men referred for vasectomy, and sperm nuclear elements were determined by X-ray microanalysis. Sperm head zinc concentrations, expressed as the ratio Zinc to Sulphur, were significantly higher in ejaculated than in vasal sperm. A physiological sperm nuclear zinc uptake is discussed in relation to sperm chromatin decondensation.