"Contractile interstitial cells" in pulmonary alveolar septa: a possible regulator of ventilation-perfusion ratio? Ultrastructural, immunofluorescence, and in vitro studies.

In the lungs of healthy rats, humans, lambs, and monkeys, about 50% of the alveolar interstitial cells-resembling fibroblasts-contain bundles of fibrils measuring 30-80 A in diameter. Immunofluorescence studies on frozen sections of rat lung demonstrate that many interstitial cells bind sera containing antiactin antibodies. On account of these two sets of findings and our additional in vitro studies suggesting alveolar tissue contraction due to hypoxia or epinephrine, we postulate that the alveolar septa contain contractile cells different from that of smooth muscle. For these cells we propose the name of "contractile interstitial cells." Such cells lie within the thick portion of the air-blood barrier and around the pre- or postcapillary vessels. Hence it is possible that they play a role in the autoregulation of ventilation/perfusion (V/Q) ratio, particularly in hypoxic pulmonary hypertension. These findings, demonstrating a contractile system other than bronchial and arterial smooth muscle, suggest that the alveolus should no more be conceived as a passive "organ."

Role of cerebrospinal fluid pleocytosis and Haemophilus influenzae type b capsule on blood brain barrier permeability during experimental meningitis in the rat.

The influence of leukocytes and Haemophilus influenzae type b (Hib) capsule on blood brain barrier permeability (BBBP) to circulating 125I-albumin in normal and leukopenic rats was assessed after intracisternal inoculation of encapsulated (Rd-/b+/02) or unencapsulated (Rd-/b-/02) isogenic strains of Hib. Both normal and leukopenic animals had increased BBBP 18 h after inoculation, with normal rats demonstrating significantly increased BBBP after challenge with the encapsulated strain. Despite cerebrospinal fluid (CSF) pleocytosis in normal rats, CSF bacterial concentrations were not lower. Normal rats cleared unencapsulated Rd-/b-/02 more effectively than leukopenic rats, with BBBP correlating with CSF bacterial density and not leukocyte concentrations. Challenge with heat-killed Rd-/b+/02 resulted in increased BBBP in both normal and leukopenic rats, with greater BBBP at higher bacterial concentrations. The data suggest: (a) significant increases in BBBP occur in the near absence of CSF leukocytes; (b) CSF leukocytes can augment changes in BBBP; (c) type b capsule inhibits host clearance mechanisms within the CSF; and (d) BBBP appears to correlate with bacterial concentrations within the CSF.

Opioid antagonist detoxification under anaesthesia versus traditional clonidine detoxification combined with an additional week of psychosocial support: a randomised clinical trial.

BACKGROUND: While detoxification under anaesthesia accelerates the detoxification procedure, there is a lack of randomised clinical trials evaluating its effectiveness compared to traditional detoxification procedures, and a lack of data on long-term abstinence. METHODS: Prospective randomised clinical trial. Analysis by intention to treat and per protocol. SETTING: Specialised substance abuse unit in a psychiatric teaching hospital and an intensive care unit of a general hospital. PARTICIPANTS: Seventy patients with opiate mono-dependence requesting detoxification: 36 randomised to RODA (treatment as allocated received by 26) and 34 randomised to classical clonidine detoxification (treatment as allocated received by 21). MAIN OUTCOME MEASURES: Successful detoxification, safety and self-reported abstinence at 3, 6 and 12 months after detoxification. RESULTS: Socio-demographics were similar in both groups at baseline. No complications were reported during or after anaesthesia. According to the intention to treat analysis, 28/36 (78%) RODA patients and 21/34 (62%) of the clonidine group successfully completed the detoxification process (p=0.14). In the intention to treat analysis, 30% of RODA patients were abstinent after 3 months compared to 14% in the clonidine group (p=0.11). No difference was found at 6 and 12 months (both groups showed less than 5% abstinence after 12 months). The per-protocol analysis showed similar results with no statistical differences either for ASI mean scores or for the SF36 questionnaire. CONCLUSION: Although the detoxification success rate and abstinence after 3 months were slightly better for the RODA procedure compared to clonidine treatment, these differences were not statistically significant and disappeared completely after 6 and 12 months.

Nonmalignant monoclonal immunoglobulinemia, pernicious anemia and gastric carcinoma. A model of immunologic dysfunction. Report of two cases and review of the literature.

The association of an autoimmune disease with a monoclonal immunoglobulin is not exceptional and most probably results from a dysfunction of the immunologic apparatus. This study describes two patients with monoclonal immunoglobulin A (IgA) and M (IgM) gammopathy, respectively, in whom pernicious anemia and finally gastric carcinoma developed. One patient had autoantibodies to gastric parietal cell and to thyroid microsomal antigen which could not be identified with the M-component. This observation, together with the fact that pernicious anemia occurred in one case before and in the other case after the discovery of M-component, suggests that different clones of cells were responsible for both disorders. Sixteen cases in which the patients had the same association have been collected from the literature and the data are compared with ours.

Outbreak of Salmonella braenderup gastroenteritis due to contaminated meat pies: clinical and molecular epidemiology.

OBJECTIVES: To determine the epidemiologic, clinical and molecular characteristics of an outbreak of severe gastroenteritis due to the ingestion of meat pies highly contaminated with Salmonella braenderup. METHODS: In October 1993, we observed an outbreak of Salmonella braenderup gastroenteritis that occurred in the Lausanne area, Canton de Vaud, Switzerland. Cultures of suspected food products, of samples at the incriminated food factory and from workers, as well as a case-control study, were used to determine the source of the epidemics. Ribotyping of representative Salmonella braenderup strains was performed to define the molecular epidemiology. The clinical characteristics of this infection were determined by using a standardized interview performed during and 6 months after the outbreak in 156 of 215 identified patients. RESULTS: The outbreak resulted from the ingestion of pies, heavily contaminated (> 106 CFU/g) with a strain of Salmonella braenderup. The contamination was due to mishandling and recycling of jelly poured on top of the products. According to its ribotype and plasmid characteristics, this strain had not been isolated previously in Switzerland. Ten of the 24 workers of the incriminated food factory were shedding the epidemic strain in their stools, and one of them reported gastroenteritis 3 weeks before the beginning of the outbreak. The estimated attack rate in the exposed population was 7.5%. The median incubation time was 18 h. Among 127 adult patients studied, 98% had diarrhea, 95% abdominal pain, 74% fever > or = 38.5 degrees C, 69% nausea and 35% vomiting. One patient developed prosthetic valve endocarditis, and one reactive arthritis. Long-term complications were not identified, although 12 patients complained of irritable bowel syndrome and 24 of unusual asthenia lasting for more than 6 weeks after infection. Children had more severe signs and symptoms compared to adults, and six of 29 needed hospitalization. CONCLUSIONS: This study showed that ingestion of food highly contaminated with Salmonella braenderup resulted in severe but typical gastroenteritis and indicated mishandling of food during manufacture as the cause of this outbreak.

Deficient phagocytosis secondary to breakdown of opsonic factors in infected exudates.

Pleural empyema, a clinical entity characterized by the simultaneous presence of large number of PMNLs and viable bacteria, is a biological paradox which has not been fully explained yet. Our preliminary studies suggest that receptor and bactericidal functions of PMNL isolated from purulent exudates, can be close to normal in this condition. Supernatants of these empyemas however have been shown to be low in heat labile opsonic activity and complement hemolytic activity. These observations have been extended by the demonstration of breakdown of IgG, C3 and factor B in infected pleural effusions as opposed to pleural fluids obtained under other conditions. The breakdown of Ig and C3 seems to be enzymatic and to occur, at least for C3, even in the absence of Ca and Mg ions: thus, direct cleavage of C3, possibly by PMNL enzymes, has to be postulated to explain these results. Present work in our laboratory is trying to explore this possibility.

Validity of resting myotonometric assessment of lower extremity muscles in chronic stroke patients with limited hypertonia: a preliminary study.

The aim of this preliminary study was to examine the validity of a recently-introduced tool (MyotonPRO) for the assessment of mechanical parameters of the main lower extremity muscles in patients with chronic stroke. Thigh and shank muscles of 20 stroke patients with limited hypertonia (11 men and 9 women; mean age: 52±11yrs) and 20 healthy controls (11 men and 9 women; mean age: 53±10yrs) were bilaterally evaluated with (i) MyotonPRO for muscle stiffness, tone and elasticity, (ii) ultrasonography for muscle and subcutaneous thickness, and (iii) dynamometry for isometric muscle strength. MyotonPRO parameters of stroke patients were reassessed a week later (inter-day test-retest design). For all the investigated muscles, MyotonPRO variables did not differ between the more affected and the less affected side of patients (P>0.05 for main side effect), and neither differed between patients and controls (P>0.05 for main group effect), except for gastrocnemius medialis stiffness that was higher in patients (300±51N/m) than in controls (281±29N/m; P<0.05). Thigh muscle stiffness was negatively correlated to subcutaneous thickness (r=-0.84 for the vastus lateralis; P<0.001), while only tibialis anterior stiffness and tone correlated positively with muscle thickness (both r=0.46; P<0.01). Test-retest reliability of MyotonPRO parameters was adequate, except for muscle elasticity. The validity of MyotonPRO for the evaluation of thigh muscles in chronic stroke patients is partially challenged by the poor discriminant ability and by the considerable impact of subcutaneous tissue thickness (sex-dependent) on mechanical parameters. The potential validity of MyotonPRO for the assessment of shank muscles requires further investigation.

[Acute epiglottitides in the adult]. / Les épiglottites aiguës de l'adulte.

Two adults were admitted to the University Hospital of Geneva with acute Haemophilus influenzae type b epiglottitis. The disease was characterized by rapid progression of sore throat, upper dysphagia, fever and dyspnea. Acute upper airway obstruction required emergency tracheotomy in both cases. The patients recovered under ampicillin therapy. All the 100 cases from the literature for which clinical data were available have been analyzed:--Epiglottitis in adult is not exceptional.--Haemophilus influenzae type b is the most common infective organism documented, and was found in all positive blood cultures but one.--The typical presentation is severe sore throat, with upper dysphagia, fever and dyspnea.--Clinical course is rapid and serious, and acute respiratory distress develops in 57% of cases; overall mortality is 27%.--Emergency routine tracheotomy appears to be the most reliable treatment.

Use of norfloxacin for prevention of symptomatic urinary tract infection in chronically catheterized patients.

Thirty-four elderly inpatients with long-term urethral catheters were randomly assigned to receive either norfloxacin (200 mg/day) or placebo in a double-blind study with cross-over after three months. Twenty-three patients completed the entire study. Norfloxacin treatment was associated with a persistent decrease in gram-negative isolates (p < 0.005) and the acquisition of gram-positive norfloxacin-resistant flora. It also resulted in a highly statistically significant reduction of symptomatic urinary tract infections (1 vs. 12, p < 0.02), a decrease in catheter-associated local complications, obstructions and leakage (p < 0.05) and an improvement in the patients' general condition (p < 0.001). In conclusion, within the conditions of the present study, long-term suppression of gram-negative bacteriuria by norfloxacin reduced the incidence of catheter-related urinary tract infection and associated morbidity.

Magnitude of bacteremia and complement activation during Neisseria meningitidis infection: study of two co-primary cases with different clinical presentations.

Two co-primary cases of schoolchildren with acute meningococcal disease due to infection with Neisseria meningitidis serogroup B are described. The first patient presented with septic shock and purpura fulminans, bacteremia greater than 10(5) organisms/ml blood, low C3 and factor B levels and an elevated level of C3d. The second patient had meningitis, negative blood cultures, normal levels of serum complement components but more than 10(4) organisms/ml in CSF. A comparison of the quantitative bacteriology data and complement profiles for these patients suggests that the degree of activation of complement during meningococcemia is directly related to the number of organisms in the blood. This association may determine the different clinical syndromes.

Contribution of lipopolysaccharide to pathogenicity of Haemophilus influenzae: comparative virulence of genetically-related strains in rats.

The elaboration of type b capsule plays an important role in determining virulence of Haemophilus influenzae but the contribution of lipopolysaccharide to pathogenicity of this organism remains undefined. Using DNA from a virulent type b H. influenzae donor strain and a capsule-deficient recipient (Rd:01), we constructed capsular transformants having lipopolysaccharide characteristics either similar to (strain Rd/b+:01), or different from (strain Rd/b+:02), the recipient strain. These two type b transformants had similar type b capsule and outer membrane proteins. Comparative virulence studies in rats showed that strain Rd/b+:02 was more virulent than Rd/b+01 as assessed by magnitude of bacteraemia, incidence of meningitis and mortality. Similarly, strain Rd/b-:02 exhibited greater pathogenicity in C3-depleted rats than its genetically-related strain Rd:01. We conclude that lipopolysaccharide composition plays a significant role in mediating the potential of H. influenzae to cause invasive infections. In addition, the findings suggest that there is linkage of virulence genes involved in lipopolysaccharide and capsule expression.

[Hypocalcemia and myelofibrosis: an unrecognized association]. / Hypocalcémie et myélofibrose: une association méconnue.

Observation of a case of myelofibrosis with myeloid metaplasia of liver and spleen associated with hypocalcemia led us to investigate whether this association was fortuitous. We retrospectively analyzed the data of 30 patients with myelofibrosis and identified 9 patients with hypocalcemia out of 22 in whom the plasma calcium level corrected for serum protein could be obtained, i.e. a prevalence of hypocalcemia of 41%. The spleen was significantly larger in the patients with hypocalcemia than in those with normal plasma calcium level, suggesting that hypocalcemia was related to the duration of the disease. In 5 patients with hypocalcemia, biological and/or morphological evidence of osteomalacia was found. It is concluded that an association exists between myelofibrosis and hypocalcemia, possibly as a consequence of a disturbed vitamin D metabolism.

Participation of complement in host defense against capsule-deficient Haemophilus influenzae.

To investigate the role of complement in immunity to capsule-deficient Haemophilus influenzae, rats were depleted of C3 with cobra venom factor and challenged with three different strains of capsule-deficient H. influenzae. Two of them (Rd and U1) did not elaborate type b capsular antigen, whereas the other (S2) elaborated 0.16% of the amount made by its type b parent strain. Depletion of C3 significantly enhanced early intravascular bacterial survival after intravenous inoculation and strikingly increased the susceptibility of rats to infection with capsule-deficient H. influenzae. After intraperitoneal inoculation with strain Rd or U1, C3-depleted rats developed bacteremia, whereas control rats did not; challenge with strain S2 resulted in transient bacteremia in normal rats and in death in C3-depleted animals. To determine whether the greater virulence of strain S2, as compared with strain Rd or U1, was accounted for by the small amounts of capsular antigen it elaborated, we also compared its relative virulence to that of three genetically closely related capsule-deficient variants elaborating either small amounts of type b capsule or producing no detectable b antigen. No difference in virulence was observed among these four variants; all C3-depleted rats inoculated developed bacteremia of similar magnitude followed by similar mortality rates. These studies demonstrate a significant role for complement in host defense mechanisms against capsule-deficient H. influenzae and suggest that interstrain differences of virulence are not attributable to residual elaboration of small amounts of type b capsule.

Surface determinants of Haemophilus influenzae pathogenicity: comparative virulence of capsular transformants in normal and complement-depleted rats.

In an assessment of the contribution of different capsular polysaccharides to the pathogenicity of Haemophilus influenzae, the virulence of H influenzae strain Rd and of a series of capsular transformants (types b, c, d, and f) of strain Rd was compared and in normal and complement-depleted rats. After intraperitoneal inoculation, the encapsulated transformants were strikingly more virulent than strain Rd, although their pathogenicity varied; type b was the most virulent, type c the next most virulent, type f less virulent, and type d the least virulent. C3 depletion enhanced the susceptibility of rats to systemic infection but did not influence the relative virulence of the transformants. Comparative studies of clearance showed efficient intravascular survival of type b, c, and f transformants but not of the type d transformant or strain Rd; C3 depletion enhanced the intravascular survival of type d. Further analysis of the capsular transformants revealed differences in the electrophoretic characteristics of their lipopolysaccharides. These studies indicate that elaboration of a unique capsular polysaccharide may not be a sufficient explanation for the greater virulence of H influenzae type b and that lipopolysaccharide may contribute to the mediation of the differential pathogenicity of the various serotypes.

[The regulation of plasma aldosterone in hemodialysis patients]. / Contrôle de l'aldostérone plasmatique chez les patients en hémodialyse.

The role of potassium in regulating plasma aldosterone has been studied in 7 patients with end-stage renal disease undergoing hemodialysis. Plasma renin activity (PRA), plasma aldosterone, cortisol, sodium and potassium, and total potassium loss were measured before and after two sessions of dialysis in each patient. The only difference between the two sessions was the potassium content of the dialysate (4 mmol/l versus l mmol/l). Plasma potassium, potassium pool and plasma aldosterone decreased significantly when the patients were dialyzed with a l mmol/l K bath. In contrast, the same parameters remained unchanged when the patients were dialyzed with a 4 mmol/l K bath. Irrespective of the dialysate used, there were no differences either in changes in body weight and PRA, or in plasma sodium and cortisol levels, before and after dialysis. In conclusion, in patients with end-stage renal disease, potassium predominates over PRA and volume depletion in the regulation of plasma aldosterone.

[Acute atropinic syndrome caused by abuse of anti-asthmatic cigarettes (Datura stramonium)]. / Syndrome atropinique aigu par abusif de cigarettes anti-asthmatiques (datura stramonium).

Over a 3-month period four patients (3 males and 1 female) aged 17 to 23 were admitted to an emergency unit with an acute anticholinergic syndrome. All of them had ingested aniasthmatic cigarettes containing Datura stramonium leaves for psychedelic purposes. The clinical features were characterized by striking peripheral signs of anticholinergic inhibition associated with central nervous system manifestations such with central state, hallucinations and abnormal behaviour. One patient had to be treated with physostigmine salicylate. The other three received supportive care only. The central and peripheral symptomatology subsided gradually over 12-48 hours. All four patients had more or less extensive amnesia regarding the acute toxic phase. Based on these observations, the possible causes, differential diagnosis and treatment of acute atropinic intoxication are reviewed. The discussion also considers the problem of abuse of "over-the-counter" atropine containing preparations.

[Angioimmunoblastic lymphadenopathy. 8 cases and review of the literature]. / Lymphadénopathies angio-immunoblastiques. Observation de 8 cas et reveu de la littérature.

Eight cases of angio-immunoblastic lymphadenopathy were recently diagnosed at the University Hospital of Geneva. The disease was characterized by generalized adenopathy, hepatosplenomegaly, fever, and sometimes skin rash. Six patients had polyclonal dysproteinemia and two displayed autoimmune disorders, e.g. Coombs' positive hemolytic anemia. Lymph node biopsy was a decisive pointer for the diagnosis. Four patients died, two of them from immunoblastic lymphoma. Four other patients are in remission, the longest follow-up being 91 months. Analysis of 213 cases from the literature shows the following features:--Males and females are equally affected, with a predominance after the age of 50.--The onset is characterized by constitutional symptoms (75%) and fever (65%), sometimes following exposure to drugs.--The signs are generalized adenopathy (91%), splenomegaly (66%), hepatomeagly (65%), and skin rash (46).--Polyclonal hypergammaglobulinemia (76%) is found, together with anemia (78%) which is often autoimmune in origin (58%).--The course is often unfavourable and the mortality is over 55%, largely due to opportunistic infections and/or development of immunoblastic lymphoma.