Non-invasive diagnosis of chronic beryllium disease in workers exposed to hazardous dust in Israel.

OBJECTIVES: Chronic beryllium disease (CBD) is caused by prolonged occupational exposure to beryllium and is characterised by various clinical presentations, mostly pulmonary. The inflammatory process involves non-caseous granulomas and proliferation of CD4+ cells. CBD is diagnosed by lung biopsy showing tissue granuloma formation, and by the beryllium lymphocyte proliferation test (BeLPT) for past exposure and sensitisation to beryllium. The induced sputum (IS) technique was developed for diagnosing asthma, chronic obstructive pulmonary disease and interstitial lung diseases. A CD4/CD8 ratio >2.5 in T cells from IS is a positive result for granulomatous lung diseases. We previously revealed that dental technicians are exposed to excessive levels of beryllium. The efficacy of IS (CD4/CD8 >2.5) and BeLPT in diagnosing CBD in 17 workplaces where beryllium was present was evaluated. METHODS: All consecutive patients with a clinical suspicion of CBD referred to our institution for diagnosis and management were enrolled. Results of the gold standard lung biopsy with BeLPT were compared to the non-invasive IS+BeLPT. Kappa and McNemar tests evaluated agreement levels. Correlations between demographic and clinical parameters and a confirmed diagnosis of CBD were analysed. RESULTS: The two approaches were compared in 57 of 98 subjects. There was a high level of agreement (kappa 0.920) between IS+BeLPT and biopsy+BeLPT. IS+BeLPT had a specificity of 97.3% and sensitivity of 87.5%. 21 of 87 exposed workers (24%) had CBD, of whom 12 were dental technicians (p=0.044 dental technicians versus all other occupations). CONCLUSIONS: This study demonstrated that the CD4/CD8 ratio in IS together with positive/negative BeLPT findings can be used in diagnosing CBD.

Malignant fibrous histiocytoma complicating mitral valve replacement.

A 67 year old woman developed a fatal febrile illness 8 years after mitral valve replacement for rheumatic valvular heart disease. The final disease persisted for 1 year and was characterized clinically by weakness, weight loss, congestive heart failure and multiple embolic events to the central nervous system and abdominal organs. The source of the emboli was a tumor, malignant fibrous histiocytoma of the left atrium, originating from the anulus fibrosus around the covered base of the prosthetic valve. This unique case suggests the possibility that chronic exposure to materials, such as Dacron, covering prosthetic valves may induce local malignant tumors.

[Stupor due to sleep apnea syndrome after total knee replacement].

Obstructive sleep apnea syndrome is defined as a condition of repeated episodes of apnea and hypopnea during sleep, accompanied by excessive daytime sleepiness. This syndrome is common among the adult population, and is related to an increased risk for significant complications, during and immediately after surgery. Often, this condition is undiagnosed, and is not considered in the pre-operative evaluation. Therefore, it is highly important to recognize this syndrome in patients who are scheduled for elective surgery, and provide appropriate management, in order to avoid life-threatening exacerbation in the perioperative period. Although this syndrome is common, there is low awareness of its expression in elective surgery in-patients. We present a case report of a patient who suffered from obstructive sleep apnea related respiratory distress following total knee replacement surgery.

CCAAT/Enhancer binding protein ß controls androgen-deprivation-induced senescence in prostate cancer cells.

The processes associated with transition to castration-resistant prostate cancer (PC) growth are not well understood. Cellular senescence is a stable cell cycle arrest that occurs in response to sublethal stress. It is often overcome in malignant transformation to confer a survival advantage. CCAAT/Enhancer Binding Protein (C/EBP) ß function is frequently deregulated in human malignancies and interestingly, androgen-sensitive PC cells express primarily the liver-enriched inhibitory protein isoform. We found that C/EBPß expression is negatively regulated by androgen receptor (AR) activity and that treatment of androgen-sensitive cell lines with anti-androgens increases C/EBPß mRNA and protein levels. Accordingly, we also find that C/EBPß levels are significantly elevated in primary PC samples from castration-resistant compared with therapy-naive patients. Chromatin immunoprecipitation demonstrated enhanced binding of the AR to the proximal promoter of the CEBPB gene in the presence of dihydroxytestosterone. Upon androgen deprivation, induction of C/EBPß is facilitated by active transcription as evident by increased histone 3 acetylation at the C/EBPß promoter. Also, the androgen agonist R1881 suppresses the activity of a CEBPB promoter reporter. Loss of C/EBPß expression prevents growth arrest following androgen deprivation or anti-androgen challenge. Accordingly, suppression of C/EBPß under low androgen conditions results in reduced expression of senescence-associated secretory genes, significantly decreased number of cells displaying heterochromatin foci and increased numbers of Ki67-positive cells. Ectopic expression of C/EBPß caused pronounced morphological changes, reduced PC cell growth and increased the number of senescent LNCaP cells. Lastly, we found that senescence contributes to PC cell survival under androgen deprivation, and C/EBPß-deficient cells were significantly more susceptible to killing by cytotoxic chemotherapy following androgen deprivation. Our data demonstrate that upregulation of C/EBPß is critical for complete maintenance of androgen deprivation-induced senescence and that targeting C/EBPß expression may synergize with anti-androgen or chemotherapy in eradicating PC.

Splenogonadal fusion diagnosed by spleen scintigraphy.

Splenogonadal fusion (SGF) is a rare congenital malformation characterized by fusion of the spleen and a gonad (almost always the left one) frequently associated with orofacial and/or limb developmental abnormalities. Only 125 cases were reported between 1883 and 1994. This report concerns a case of SGF in a 20-yr-old woman with an accidental finding of a splenic space-occupying lesion protruding into the lower abdomen in ultrasound and CT. Radiocolloid spleen scintigraphy and SPECT proved to be the best procedure to establish the correct diagnosis of SGF. As SGF is often asymptomatic, more liberal use of splenic scintigraphy is suggested in patients with congenital limb and/or orofacial anomalies. SGF should be included among the differential diagnoses of left abdominal, pelvic or scrotal masses.

Another complication of thoracostomy--perforation of the right atrium.

Tube thoracostomy is an invasive procedure that is frequently life-saving but carries a risk of complications. We describe herein a complication not documented before-laceration of the right atrium. This occurred in a severely kyphoscoliotic patient with a markedly narrowed chest and led to his demise. This case attests to the extreme caution warranted when using trocar-type thoracostomy in patients with thoracic deformities.

Nebulized wet aerosol treatment in emergency department--is it essential? Comparison with large spacer device for metered-dose inhaler.

OBJECTIVE: To determine the efficacy of a metered-dose inhaler (MDI) with a large spacer device as compared to nebulized wet aerosols in the treatment of an unselected population with severe airflow limitation. DESIGN: Randomized, double blind, placebo-controlled trial. SETTING: University Hospital Department of Emergency Medicine (DEM). PATIENTS: Fifty patients, referred to the DEM between October 1, 1994 and March 31, 1995 with a severe, acute obstructive pulmonary event. Thirteen patients were diagnosed as having COPD; 37 patients were diagnosed as having asthma. INTERVENTION AND RESULTS: Patients received either placebo MDI through a 750-mL cone-shaped spacer (Glaxo) [2 puffs] and nebulized salbutamol aerosol 0.5 mL in 1.5 mL saline solution (group 1, n=25) or salbutamol MDI and 0.5 mL saline solution in 1.5 mL saline solution administered in the same manner as above (group 2, n=25). The above treatment was repeated three times every 15 min, unless side effects appeared. Upon enrollment into the study, the FEV1 in group 1 was 0.78+/-0.7 L (mean+/-SD), 32% of predicted, and in group 2, 0.74+/-0.51 L, 29% of predicted (p=0.83). The FEV1 values after the first, second, and third interventions were as follows: in group 1, 1.18+/-0.99 L, 1.40+/-0.8, and 1.47+/-0.79, respectively, and in group 2, 1.17+/-0.99 L, 1.46+/-1.01, and 1.54+/-0.79 (p=0.83, 0.36, and 0.48, respectively). We observed no difference in spirometric measurements between the two groups at any time. CONCLUSION: Even in the setting of the unselected group of patient referrals to the DEM for episodes of severe airflow limitation, the clinical and the objective bronchodilator responses to the administration of salbutamol are independent of the method of delivery: MDI with a large spacer vs aerosol nebulization.

Extralobar sequestration presenting as massive hemothorax.

Pulmonary extralobar sequestration is a rare anomaly, usually diagnosed during the first months of life. A case of extralobar pulmonary sequestration in an adult, manifesting itself as massive hemothorax, is presented.

Is nebulized aerosol treatment necessary in the pediatric emergency department?

BACKGROUND: Infants and small children admitted to the pediatric emergency department (PED) with acute wheezing episodes (AWE) are currently treated with nebulized wet aerosol (NWA). OBJECTIVE: To determine the efficacy of MDI with Nebuchamber (Astra AB; Lund, Sweden), a nonelectrostatic spacer device (NESD), as compared to NWA in the treatment of an unselected population of babies and small children with AWE. DESIGN: Randomized, double-blind, placebo-controlled trial. Forty-two children referred to the PED (median age +/- SD, 16 +/- 15 months) with AWE received either placebo MDI through a NESD (four puffs) and salbutamol 0.5 mL (2.5 mg) as a NWA (group I, n = 19), or salbutamol MDI and 0.5 mL of saline solution administered in the same manner as above (group II, n = 23). This treatment was repeated three times every 20 min. RESULTS: The respiratory rates (RRs) at baseline were as follows: group I, 45 +/- 11.2 breaths/min; and group II, 52.3 +/- 11.3 breaths/min (p = not significant [NS]). After the first, second, and third interventions, the percent fall from baseline of the RR were as follows: group I, 8.9, 13.1, and 17.9%, respectively; group II, 8. 6, 14.6, and 18.6%, respectively. There was no significant difference at any time in the results between the two groups. The clinical scores (CSs) at baseline were as follows: group I, 6.6 +/- 1.3; group II, 6.8 +/- 1.49 (p = NS). After the first, second, and third interventions, the percent fall from baseline of the CS were as follows: group I, 9.1, 17.9, and 23.2%, respectively; group II, 8. 6, 18.9, and 24.7%, respectively. These results, also, did not differ significantly at any time between the two groups. Hospitalization rate and side effects did not differ between the two groups. CONCLUSIONS: We conclude that even in the group of unselected very young children (mean age < 2 years) with AWE, the use of MDI with NESD is at least as effective as the use of NWA. As opposed to data from an adult population, no plateau was reached in the dose-response curve using the above doses over time.

Salbutamol metered-dose inhaler with spacer for hyperkalemia: how fast? How safe?

OBJECTIVE: To determine the efficacy of inhaled salbutamol (rapidly delivered, using a metered-dose inhaler with a spacer device [MDI-S]) in lowering the serum potassium levels in patients with hyperkalemia. DESIGN: A randomized, double-blind, placebo-controlled trial. PATIENTS: Seventeen chronic renal failure patients referred to the Nephrology Unit between October 1, 1997 and March 31, 1998 for hemodialysis were randomized. INTERVENTION AND RESULTS: Group 1 received salbutamol followed by a placebo. Group 2 received a placebo followed by salbutamol. Each patient inhaled 1,200 microg salbutamol or a placebo through an MDI-S within 2 min. Blood samples were obtained repeatedly before inhalation and after 1, 3, 5, 10, and 60 min. The pulse rate and blood pressure were repeatedly measured. Insulin levels were examined in a subset of patients (n = 10) before, and 1 and 5 min following inhalation. Salbutamol's known side effects, palpitation, tachycardia tremor, and headache, were recorded. Potassium levels rose after 1 min following the completion of treatment and then decreased steadily thereafter. A rise of > or = 0.1 mEq/L was seen in 10 of 17 patients (59%) during the treatment period and there was no change (0%) seen during the placebo period (p < 0.0001). Within 3 min after inhalation of salbutamol, potassium levels declined as a function of time. Potassium levels in those patients taking the placebo did not change as a function of time (p < 0.001). The difference between the placebo and the salbutamol-treated periods reached significance after 5 min (p < 0.05). The serum glucose levels rose following inhalation of salbutamol, with a significant rise after 3 min. The heart rate rose significantly within the first 5 min following inhalation. Serum insulin levels remained unchanged 1 min after inhalation; however, after 5 min, a significant elevation was detected. CONCLUSION: Salbutamol inhalation of 1,200 microg, using an MDI-S, has a relatively rapid onset of action that induces a consistent reduction in serum potassium levels, starting 3 to 5 min following delivery. Unexpectedly, a paradoxical elevation was detected in serum potassium levels in the first minutes following inhalation. This effect, although minor (0.15 mEq/L above baseline), may cast some doubt on the role of salbutamol inhalation as the first treatment for excessive hyperkalemia.

Primary pulmonary hypertension in Israel: a national survey.

OBJECTIVES: To characterize the incidence of patients with primary pulmonary hypertension (PPH) in Israel and their outcomes. METHODS: We have evaluated retrospectively all the patients in Israel in whom PPH was diagnosed between the years 1988 and 1997. We looked at medical history, hemodynamic data, pulmonary function and gas exchange, and demographic variables. Patients were followed up for survival until November 1997. Life table analysis and Kaplan-Meier statistics were used to estimate the overall survival distribution. Regression analysis was used to examine the relations between survival and selected variables. RESULTS: Overall, we found 44 patients with PPH. The estimated incidence of PPH in Israel is 1.4 new cases per year per million population. The mean (+/- SD) age at diagnosis was 43 +/- 13 years. In the Jewish population, PPH was more frequent among immigrants from Europe and the United States. The mean interval from the onset of symptoms to diagnosis was 3 years (median, 2 years). The median survival time was 4 years. The 1-year, 3-year, and 5-year survival rates were 82%, 57%, and 43%, respectively. The major variables influencing the survival rate were the following: interval from symptom onset to diagnosis; and hemodynamic measurements (ie, mean pulmonary artery pressure, mean right atrial pressure, and cardiac index). In comparison to rates discerned from the National Institutes of Health registry data, the survival rate in Israel is somewhat better and prognosis is influenced by similar hemodynamic variables. CONCLUSION: PPH is a rare and fatal disease in Israel. New therapeutic modalities such as prostacyclin therapy and lung transplantation may improve survival among patients with this malignant disease.

Rectal colonization with vancomycin-resistant enterococci among high-risk patients in an Israeli hospital.

The prevalence of rectal carriage of vancomycin-resistant enterococci (VRE) in two high-risk populations--61 patients admitted to ICU and 92 patients on renal dialysis--was studied longitudinally over a period of six months in a 650-bed general hospital. ICU patients were swabbed weekly and dialysis patients monthly. Enterococcal isolates were fully identified using the ATB identification system, and MICs were determined according to the NCCLS recommendations. Enterococci were isolated in 52 (83.6%) ICU patients and 86 (93.4%) dialysis patients. VRE were recovered at least once in 14 (27%) ICU patients and four (4.8%) dialysis patients. All VRE isolates (MIC of vancomycin > or = 256 micrograms/mL) were resistant to teicoplanin (MIC > or = 32 micrograms/mL; vanA phenotype), 87.5% were ampicillin-resistant, and 92% showed high-level resistance to gentamicin; 88% were E. faecium. The main risk factors for acquisition of VRE included duration of hospitalization in the six months preceding entry into the study and during the survey (P = 0.009 and 0.007 respectively, for ICU patients), and duration of antibiotic administration (P = 0.005, for ICU patients). The impact of vancomycin was most prominent (P = 0.005 for receipt and 0.06 for duration of administration, in ICU patients). Six of the 18 VRE carriers developed bacteraemia, six isolates being vancomycin-susceptible and one vancomycin-resistant (one patient had both). In this study, the first in Israel, a low rectal carriage rate occurred in renal dialysis patients and antibiotic use was the most important risk factor for VRE colonization.

Idiopathic pulmonary hemosiderosis, complete heart block and celiac disease.

A 24-year-old male with recurrent hemoptysis due to idiopathic pulmonary hemosiderosis and celiac sprue developed infranodal heart block necessitating implantation of a pacemaker. A possible common underlying mechanism is discussed.

Knowledge and attitudes of children towards cigarette smoking and its damage.

The present study reports the results of knowledge and attitudes of 280 children (mean age = 6.9 +/- 0.75 years) towards cigarettes and smoking. Subjects were divided into two groups: (I) children of parents who smoked (n = 178) and (II) children whose parents did not smoke (n = 102). The scoring for knowledge in the topics of cigarettes, smoking and the consequences was similar in the two groups (6.2 +/- 2.2 vs 6.1 +/- 2) (N.S.). The differences between the two groups were obvious and significant (p = 0.001) in their attitude towards smoking and its damage; children in group I displayed tolerant attitudes towards smoking even though they knew its consequences in comparison with the children of group II (6.1 +/- 2.4 vs 7.0 +/- 2.2). Without any exceptions among the children of the two groups, 7.4% believe that even at this young age they will begin to smoke one day. In addition, 2.1% pointed out that it is possible they will belong one day to the smokers' group. Of the population study, 90.2% believe that instruction about smoking damage should be included starting from the first grade of elementary school, and certainly, it should be at the level which will be understandable for them. As the pupils' knowledge about the consequences of smoking was lacking, we could add that the important topic of smoking and the damage it can inflict should be taught in all schools from the level of the first grade and during all subsequent years of study. Pupils should be familiar with all aspects of negative consequences caused by cigarette smoking. This knowledge may have influence upon their attitude towards smoking and smokers. More studies should be done to find what may change the positive attitudes of these pupils towards cigarettes and smoking.

Fatal asthma: where did we go wrong?

Vivid descriptions of life-threatening asthma attacks have persisted into modern medicine since antiquity. Asthma is characterized by airway hyperresponsiveness--a condition of an exaggerated bronchoconstriction in response to a variety of stimuli (irritants and triggers). Over the past decade it has become clear that in asthma significant inflammation occurs in the airways. Airway hyperresponsiveness and the clinical asthma symptomatology may be at least in part dependent on the inflammation generated by cell mediated immune mechanisms, including T cells, macrophages as well as mast cells and eosinophils in the airways. However, the recent advances in the understanding of the pathogenesis and pathophysiology of asthma, new modes for the diagnosis of the disease and the development of various therapeutic options have not been accompanied by increased survival rate. On the contrary, a gradually rising death rate from asthma has been reported worldwide. The reasons for this are not completely understood. Controversy exists whether an increase in the prevalence or the case fatality rate or both are the main cause of the reported rise in asthma death rate. Genetic, environmental and psychological factors have also been implicated. One has to consider the poorly controlled state in which some patients arrive at emergency wards, the possible delay in adequate therapy due to psychological and socioeconomic factors and also the information implicating iatrogenic factors among the possible explanations for increased asthma mortality. It is imperative to improve patient and family education to increase awareness. Conflicting results in the medical literature regarding the medical therapy of asthma impose a great responsibility on the practising physician. It is necessary to improve physician knowledge of the modern therapeutic strategies in asthma to gain better control of the disease. Pending further clarification as to optimal management of asthma, and forthcoming new and novel treatment, management should rely on current guidelines, emphasizing the role of antiinflammatory therapy in severe asthma. It is desirable to improve emergency services to deliver expert care in life-threatening conditions as soon as possible.

[Ethical considerations in mass casualty situation].

Mass casualty is a situation, in which, the physician is compelled to make critical decisions under heavy pressure load, due to severe shortage in time, personnel and information. This task is extremely difficult to fulfill, as the physician has to consider not only professional tools, but needs also to utilize ethical principles, in order to provide the best possible care to most of the casualties who might benefit from it. By definition, in the mass casualty situation the medical facility lacks temporarily the ability to deliver effective therapy to all, as the injured outnumber the medical capacity for a given time. The ethical conflicts and dilemmas that arise during such an event are enormous. Amazingly, only a few articles have addressed the issue of ethical considerations during mass casualty situation. Ethical decision making is based on four principles: beneficence, nonmaleficence, autonomy and justice. Compassion, trustworthiness, discernment and integrity are the four qualities required from those practicing medicine. These virtues should be manifested in mass casualty situations, one of the most demanding situations a physician may face.

[Tuberculous lymphadenitis in a general hospital].

All cases of tuberculous lymphadenitis admitted over a 43-year period (1951-1993) were surveyed. The diagnosis was validated in 188 cases. The incidence was 2.74 cases per year, but there was a cluster of 94 cases in the first 20 years. 50.8% had local signs alone, while 36.4% had both local and systemic signs. Nodes affected showed either painless or painful swelling, and sometimes there was drainage. Cervical nodes were affected most frequently, and the commonest general symptom was fever, followed by fatigue. In 28.8% there was pulmonary tuberculosis, in 14.4% other forms of extrapulmonary tuberculosis, and in 9.3% only active tuberculous lymphadenitis. Most of the patients had immigrated to Israel from eastern Europe and the Yemen. Though tuberculous lymphadenitis has become infrequent, it is still the commonest form of extrapulmonary tuberculosis. A high index of suspicion is needed to diagnose accurately and treat this potentially curable condition.

[Cat scratch disease].

Cat scratch disease (CSD) is usually manifested in children and young adults as a benign, chronic self-limited lymphadenopathy. However, various atypical presentations have been described, especially in immunocompromised hosts. 1 of 5 cases of CSD diagnosed here during 1985-1993 is presented. In 3 cases the diagnosis was supported by lymph node biopsy in which the organisms were visualized by Warthin-Starry silver impregnation staining. Recent publications indicate that Afipia felis and Rochalimaea henselae, both Gram-negative bacilli, were isolated from infected lymph nodes in CSD. The usual benign course does not necessitate antibiotic therapy. The antimicrobial agents effective in cases with systemic symptoms were rifampicin, ciprofloxacin, trimethoprim-sulfamethoxazole and gentamicin. In view of the increasing number of cats, an increased incidence of CSD may be expected. The mechanism of transmission from cat to man is still unknown. Fleas or ticks may be involved. Hopefully, recent advances in the identification of the causative organisms may lead to the development of serological tests, reducing the need for skin testing and lymph node biopsy.

[Splenic hemorrhage masquerading as myeloproliferative disease].

While blunt trauma to the spleen may result in various clinical features, it sometimes may not cause symptoms. A 59-year-old man presented with fever 2 weeks after minor chest trauma. Initial investigation suggested a myeloproliferative disorder. However, abdominal ultrasonography established the diagnosis of subcapsular and intrasplenic hemorrhage. Management was conservative and he was discharged after 13 days.

[Is routine monitoring of theophylline blood levels really effective?].

Theophylline is widely used by patients with asthma and chronic obstructive pulmonary disease as a bronchodilator. The therapeutic range is relatively narrow: 10-20 mcg/ml. In a survey of 344 blood samples from 290 patients over a period of 12 months, 60% had levels lower than 10 mcg/ml, and only 28% were within the therapeutic range. This was especially the case among those using oral preparations. Our data raise several questions concerning the individualization of theophylline dosage, the effectiveness of its routine blood monitoring, and the implications of these results for ambulatory patients who are possibly being under treated.