Diabetes mellitus following pentamidine-induced hypoglycemia in humans.

Four patients, treated with pentamidine because of Pneumocystis carinii pneumonitis, displayed severe fasting hypoglycemia during this treatment. Diabetes mellitus appeared later, requiring insulin therapy in the three of them who survived more than a few weeks. The metabolic study, performed in two cases during the hypoglycemic period, demonstrated inappropriately high insulin levels in the postabsorptive state. 28 +/- 1 microunits/ml (blood glucose 41 +/- 4 mg/dl) and 86 +/- 5 microunits/ml (blood glucose 15 +/- 5 mg/dl) vs. 15 +/- 3 microunits/ml in 10 control subjects and 55 +/- 3 microunits/ml in 6 patients with a verified B-cell tumor, respectively. Poor B-cell secretory responses followed the stimulations by oral glucose (maximal increment over basal: +5 microunits/ml vs. + 40 microunits/ml in control group and +77 microunits/ml in the insulinoma group), by i.v. arginine (maximal increment + 10 and +28 microunits/ml, respectively, vs. +55 in the controls and +90 microunits/ml in the insulinoma group) and by i.v. glucagon (+10 and +23 microunits/ml, respectively) vs. +40 microunits/ml in both the control and the insulinoma groups). Plasma cortisol and glucagon, and the A-cell response to arginine were higher than normal. These high, nonsuppressible, nonstimulable insulin levels and the sequence of hypoglycemia followed by insulin-dependent diabetes mellitus is consistent with the hypothesis of a selective toxicity turned towards the B-cells. In vitro incubation of islets with pentamidine 10(-10) M produced a passive release of insulin, followed by a significant decrease in B-cell response to glucose + theophylline. It is suggested that pentamidine can induce hypoglycemia because of an early cytolytic release of insulin, and then diabetes mellitus because of B-cell destruction and insulin deficiency.

Recurrent optic neuromyelitis with endocrinopathies: a new syndrome.

We report a new syndrome that we call "recurrent optic neuromyelitis with endocrinopathies" in eight Antillean women from Martinique and Guadeloupe Ocular involvement was either monocular or binocular, whereas myelopathy was acute or subacute. In seven patients, myelopathic symptoms recurred, and in six patients, visual problems recurred. Spinal cord involvement was a consistent band-like pseudo-syringomyelic dissociated sensory loss. All eight patients had endocrinopathies consisting of amenorrhea, galactorrhea, diabetes insipidus, hypothyroidism, or hyperphagia. Spinal cord MRI revealed cavitation-like images. Various immunosuppressant treatments had little effect on the uniformly deteriorating course, ending in blindness and paraplegia. Six patients died within 5 years of onset, and an autopsy in one patient showed multiple demyelinizing lesions of the spinal cord with thickened blood vessels walls without evidence of inflammation. These cases appear to constitute a syndrome distinct from MS and from classic Devic's syndrome, not only because of the association with endocrinopathies but because of the stereotypy of the recurrences, the absence of MRI lesions in the cerebral white matter, and the unusual image of cavitation of the spinal cord. The syndrome is also distinct from HTLV-I-associated paraparesis, which is endemic in the West Indies.

Nebulized cyclosporine in the rat: assessment of regional lung and extrapulmonary deposition.

BACKGROUND: Nebulized cyclosporine (CsA) has been shown to limit lung allograft rejection as well as intramuscular (IM) CsA, with limited blood diffusion. The present study determined the pharmacokinetic parameters of nebulized CsA, by the assessment of regional lung deposition and extrapulmonary diffusion of CsA. METHODS: CsA was given either by IM injection (10 mg/kg) or by aerosol (at 10 and 25 mg/kg doses); 70 rats were killed at 25 and 50 min, and at 2, 4, 6, 8, 12, 24, or 48 hr after CsA administration. CsA levels were measured in the whole lung, in central and peripheral parts of the lung, in whole blood, kidney, and heart. The areas under the concentration time curves (AUCs) were determined. RESULTS: In blood, kidney, and heart, CsA levels were significantly higher for IM than for aerosol administrations at 10 and 25 mg/kg doses. In the whole lung, the AUC was greater for the aerosol route at 25 mg/kg doses (588 ng x hr/mg) than for the low-dose (200 ng x hr/mg) or IM administration (200 ng x hr/mg). The central to peripheral index of CsA (ratio of AUC central/peripheral part of the lung) was not significantly different for both aerosol administrations (0.63 and 0.69, respectively) and for the IM route (0.81). CONCLUSIONS: Nebulized CsA allows better pulmonary concentration than IM administration, with equivalent central and peripheral deposition whatever the mode of administration, and results in lower levels in blood, kidney, and heart.

Predictive value of cytomegalovirus DNA detection by polymerase chain reaction in blood and bronchoalveolar lavage in lung transplant patients.

BACKGROUND: Despite promising results, the efficacy of polymerase chain reaction (PCR) for clinical management of cytomegalovirus (CMV) infection in transplanted patients is still controversial. METHODS: A prospective study of CMV detection, with concurrent shell vial cultures and PCR in blood and bronchoalveolar lavage (BAL), was conducted in 13 lung transplant recipients, monitored for 15 months (range: 1-42 months). CMV DNA was detected by PCR amplification of a 406-bp fragment in the Us region and a 290-bp fragment in the immediate early region of the viral genome. RESULTS: When comparing PCR to viral culture, the sensitivity and specificity of CMV DNA detection were 100% and 65.7% in blood (n=122) and 100% and 75% in BAL (n=104). The positive and negative predictive values of PCR for a forthcoming diagnosis of CMV infection were 50% and 97% in blood, and 67% and 85% in BAL. Seventeen CMV infections were evaluated at the end of treatment: when PCR was still positive either in blood or BAL, CMV infection relapsed within 35+/-5 days; when PCR was negative, CMV infection relapsed after 142+/-57 days (P=0.01). CONCLUSIONS: Negative CMV detection by PCR strongly advocates against a forthcoming CMV infection. PCR assay seems to be a good predictor for early recurrence of CMV infection, and would be useful for monitoring the response to antiviral therapy.

Bronchoalveolar lavage in amiodarone pneumonitis. Cellular abnormalities and their relevance to pathogenesis.

To investigate the contribution of direct cytotoxicity and immune-mediated hypersensitivity to the pathogenesis of amiodarone pneumonitis, we evaluated cells recovered by bronchoalveolar lavage from 13 patients with amiodarone pneumonitis. Alveolar macrophages from all patients contained two types of abnormal inclusions: small clear vacuoles and large phagolysosomes containing phospholipid in lamellar structures, abnormalities previously attributed to direct cytotoxicity from amiodarone. However, these changes were always associated with abnormalities in the numbers and types of immune and inflammatory cells present in the lower respiratory tract, which closely resemble those seen in hypersensitivity pneumonitis associated with inhaled antigens. Following discontinuation of amiodarone and institution of corticosteroid therapy, clinical improvement correlated with a return toward normal in the pattern of inflammatory cells present in the lung, although alveolar macrophages continued to display evidence of drug-induced cytotoxicity. These findings support the possibility that a cell-mediated immune response usually plays a role in the pathogenesis of amiodarone pneumonitis, although direct cytotoxicity may predispose these patients to the development of this abnormal immune response.

Lymphocytic alveolitis after primary HIV infection with CMV coinfection.

Herein is a report of an adult case of primary HIV infection with cytomegalovirus coinfection causing cough, fever, and lymphocytic alveolitis. Primary HIV infection has not been previously reported as a cause of lymphocytic alveolitis.

Blood and alveolar lymphocyte subsets in pulmonary cytomegalovirus infection after lung transplantation.

BACKGROUND: Cytomegalovirus (CMV) pneumonitis has been shown to be associated with lymphocytic alveolitis after lung transplantation. In the present study, we investigated a series of bronchoalveolar (BAL) and blood samples, collected in the absence of rejection or acute infectious episodes. in order -1: to evaluate intra-alveolar cell population changes concomitant with CMV replication and -2: to reappraise the value of cell population analysis in the management of patients after lung transplantation. METHODS: We used flow cytometry to investigate modifications of lymphocyte subpopulations related to pulmonary cytomegalovirus infections in blood and BAL samples from a series of 13 lung transplant recipients. After exclusion of samples obtained during pulmonary rejection, bronchiolitis obliterans or acute bacterial infection, 48 blood and BAL samples were retained for analysis: 17 were CMV positive by shell-vial assay and 31 were CMV negative in blood and BAL. RESULTS: Our results demonstrate that pulmonary CMV infection is associated with a significant increase in the total lymphocyte population in BAL samples, but with minor modifications of the various lymphocyte subpopulations and a significantly higher absolute number of B lymphocytes in blood samples. CONCLUSIONS: Cytomegalovirus pulmonary infection is accompanied by only minor changes in BAL lymphocyte subpopulations. The study of BAL lymphocyte subpopulations therefore appears to be of limited clinical value in the diagnosis of pulmonary CMV infection. However, increased blood B-lymphocytes seems to be a clinical feature associated with CMV infection.

Comparison of jet and ultrasonic nebulizers for alveolar targeting of methylprednisolone.

The secondary systemic effects of oral corticosteroid therapy in chronic lung disease indicate the possible benefits of local therapy. The aim of this study was to show if alveolar targeting of a corticosteroid, methylprednisolone (MP), is possible, and to determine which type of nebulizer allows the most selective deposition into the alveoli. A jet nebulizer (Respirgard II) with 2 ml volume fill (R2), and an ultrasonic nebulizer (Ultraneb 99) with 4 ml volume fill (U4), were compared using a 40-mg dose of MP labelled 99Tcm human serum albumin. Particle size and MP-to-albumin binding were measured in the aerosol cloud. Each nebulizer was used in random order in five healthy volunteers. A dynamic posterior scan of 68 images of 15 s each was performed with a Gammatome II gamma camera during inhalation. Peripheral and central regions of interest were automatically defined with reproducible methods, and the peripheral-to-central ratio was used as a penetration index. Stomach and oropharynx activities were estimated on static anterior and static left lateral views, respectively, at the end of the examination. The mass median aerodynamic diameter (MMAD) was lower for R2 when unlabelled MP was used. The MMAD of MP+HSA was compatible with alveolar targeting. In the aerosol cloud, MP-albumin binding was 75% for R2 and 79% for U4. Peripheral and central activities at equilibrium (13-16 min) were higher with U4, but the penetration index was significantly higher with R2. Moreover, the stomach and oropharynx activities were significantly lower with R2.(ABSTRACT TRUNCATED AT 250 WORDS)

Cisplatin and vindesine for disseminated non-small cell lung cancer. Results of a prospective trial with 81 patients.

Eighty-one patients with disseminated non-small cell lung cancer (stage IV) were treated with 2 monthly cycles of initial chemotherapy combining cisplatin with vindesine. The initial chemotherapy-responding patients (CR, PR, MR) were randomized to 2 cycles or 4 cycles of maintenance chemotherapy. After initial chemotherapy, the response rate was 33% (CR, PR, MR) with 18.5% objective responses. The overall 1-year survival rate was 15% with 37% for responders as opposed to 2% for non-responders. Maintenance chemotherapy did not improve the response rate obtained after initial cycles. The small number of patients does not allow us to reach a definite conclusion on the optimum duration of maintenance chemotherapy. In the absence of large placebo versus chemotherapy randomized trials, no definite conclusion can be made on the benefit of chemotherapy in disseminated non-small cell lung cancer. This study suggests, however, that chemotherapy is associated with a significantly longer survival in responding patients.

[Surgical treatment of chronic pulmonary embolism using thromboembolectomy under extracorporeal circulation and deep hypothermia--a new approach route. 3 cases]. / Traitement chirurgical des embolies pulmonaires chroniques par thrombo-embolectomie sous circulation extracorporelle et hypothermie profonde--nouvelle voie d'abord. Trois observations.

The authors, who have successfully performed thrombectomy of the pulmonary artery under extracorporeal circulation and deep hypothermia in three patients, wish to draw attention to the principal factors of success. The decision to operate, as accepted by most surgeons, rests on the patient's functional status (stage III or IV) and on the presence of a systolic pulmonary arterial pressure exceeding 50 mmHg. Deep hypothermia combined with circulatory arrest seems to be the best method, as it improves visual control, thereby avoiding damage to the endothelium or fracture of the distal thrombi during thrombectomy. Finally, a new approach route (severing of the superior pulmonary vein, opening of the pulmonary artery and use of Volmar-Sisteron strippers) makes it possible to remove the entire thrombus, thus obtaining an almost normal pressure in the pulmonary artery. In all three patients, the complications that are mostly due to intrabronchial haemorrhage by disruption of the endothelium, fracture of the distal thrombus or pulmonary artery contusion were avoided.

[Idiopathic hypotension of the cerebrospinal fluid]. / Hypotension idiopathique du liquide céphalo-rachidien.

A case of spontaneous hypotension of the cerebrospinal fluid (CSF) is reported. A 32 years-old woman was complaining of intense orthostatic headaches. CT scan showed slit ventricles and the spinal tap showed a pressure of the CSF too low to be measured. A sample of clear CSF could only be obtained by aspiration. The patient's status improved without drugs by simply staying in bed for one week. Few similar cases have been reported. The mechanisms of this disorder still remains unknown.

[Lung transplantation]. / Transplantation pulmonaire.

Lung transplantation began to expand in 1983, after the advent of cyclosporin and the publication of the Toronto lung transplant group study. Single lung transplantation was first performed in patients with interstitial pneumopathy to be extended later to pulmonary emphysema, then to primary or secondary pulmonary arterial hypertension. Double lung transplantation provides patients suffering from chronic lung infection (e.g. cystic fibrosis) with a useful alternative to their ordinary treatment. The experience acquired throughout these years has resulted in wider criteria for patients' inclusion. More than acute rejection, bacterial infections directly condition the immediate prognosis. The frequency and severity of cytomegalovirus lung diseases lead to a discussion on the possibility of prophylactic and curative antiviral therapy. The occurrence of obliterative broncholitis, which reflects chronic lung rejection, jeopardizes the long-term results of transplantation. The functional results of the various types of lung grafting are analysed, and the position of lung transplantation in thoracic surgery is reassessed.

[Alveolar microlithiasis. Non-invasive diagnosis using alveolar lavage and technetium scintigraphy]. / Micro-lithiase alvéolaire. Diagnostic non invasif par lavage alvéolaire et scintigraphie au technetium.

A new case report of alveolar micro-lithiasis shows the diagnostic interest of two non invasive explorations to affirm a radiologic suspicion. Technetium showed calcium in the lung. The broncho-alveolar lavage, realised with a big quantity of fluid, removed the microliths. These two technics together avoid pulmonary biopsy.

[Variations in the distribution of bronchial arteries. Apropos of 72 arteriographies]. / Variations de la distribution des artères bronchiques. A propos de 72 artériographies.

Anatomic distribution of bronchial arteries was studied by arteriography, and evaluation conducted of 72 images considered as being complete. Seven frequent types of distribution were note and findings compared with those of previous studies. Frequency of collateral circulation and of anastomosis was comparable with that reported in the literature. One new distribution pattern was observed: common lower trunk, right upper intercostobronchial trunk, left upper trunk.

[Evaluation of the right ventricular function for lung transplantation. Value of the electron beam scanner]. / Evaluation de la fonction ventriculaire droite en vue d'une transplantation pulmonaire. Intérêt du scanner par faisceau d'électrons.

Several invasive or not invasive technics were used to evaluate right ventricular insufficiency associated to severe chronic pulmonary insufficiency. But none of them were very accurate and now the use of EBT appears as a real improvement. We performed a prospective study with 50 patients waiting for a lung transplantation and we compared the values of right ventricular function obtained by EBT to those obtained by nuclear medicine and catheterism. Accuracy of EBT for left ventricule evaluation has already been proved. Stroke volumes calculated by EBT in right and left ventricules are similar and this constitutes a good validation of the method for right ventricule evaluation. Correlations with hemodynamic measurements are poor and nuclear medicine technics underestimate the ejection fraction. So, EBT is recommended for right ventricular study before and after lung transplantation.

[Intralobar sequestration of the lung in an adult (type 1 of pryce). Treatment by coil embolization]. / Séquestration pulmonaire intralobaire de type pryce 1 chez l'adulte. Vaso-occlusion par spires métalliques.

A 34 year old patient presented with recurrent hemoptysis. A chest radiograph was normal. Helical CT angiogram of the chest with tridimensional reconstructions demonstrated an intralobar pulmonary vascular sequestration Pryce I-type of the right lower lobe. The angiography confirmed the diagnosis showing a large feeding artery arising from the coeliac trunk. An embolization of the feeding artery using metallic coils was performed. Transient pulmonary infarction occurred immediately after treatment. At two years follow-up, the patient remains asymptomatic. Percutaneous embolization of this rare pulmonary vascular malformation is an alternative to surgical treatment.

[Noninvasive diagnosis of alveolar microlithiasis by Tc99m-MDP scintigraphy and alveolar lavage]. / Diagnostic non invasif de la microlithiase alvéolaire par la scintigraphie aux Tc99m-MDP et le lavage alvéolaire.

In a new case of alveolar microlithiasis we report the diagnostic value of two non-invasive examinations. In agreement with the histo-chemical date, scintigraphy with technetium shows an abnormal pulmonary fixation as evidence of the presence of intra-pulmonary calcium. The demonstration of micro-lithiasis in the alveolar lavage liquid, which requires a particular technique, confirms the diagnosis and avoids an open lung biopsy.

[Report of 2 cases of pleural recurrences of surgically treated bronchogenic carcinoids. Diagnostic and therapeutic problems]. / A propos de 2 récidives pleurales de carcinoïdes bronchiques opérés. Problèmes diagnostique et thérapeutique.

Recurrence after surgery for bronchial carcinoid tumors is very uncommon in cases of typical tumors and occasionally seen in cases of atypical tumors. We observed two cases of recurrence in an unusual location, the pleura. Somatostatin analog and MIBG scinigrams were useful for diagnosis. Treatment required surgical excision of the relapsing tumor, cytoreductive hepatic surgery or hepatic arterial chemoembolization for liver metastases, chemotherapy, interferon, radionuclide therapy, and somatostatin analogs for carcinoid syndrome.

[Healing of bronchial anastomoses in single and double pulmonary transplantations]. / La cicatrisation des anastomoses bronchiques dans les transplantations uni- et bipulmonaires.

Bilateral single lung transplantation (BSLT) (the procedure of choice for double lung replacement) and single lung transplantation (SLT) have at present a low incidence of anastomotic problems. In our experience, we have recorded no death related to anastomotic problems and 4 complications occurred for 33 anastomoses with a follow up of at least 2 months. A stent was temporarily inserted for two patients. The decrease of anastomotic complications is confirmed in the literature. It is one of the reasons why the number of SLT and BSLT performed all over the world increases rapidily to the detriment of heart lung transplantation.

[Double lung transplantation. The "bilateral single" graft]. / Greffe bipulmonaire. La double unilatérale.

We present 10 cases of a new double lung transplantation technique: following, then the other, without requiring cardiopulmonary bypass. This "bilateral single" lung transplantation procures all the advantages of single lung transplantation.