Traumatic shock and electroshock: the difficult relationship between anatomic pathology and psychiatry in the early 20th century.

In the conviction that a look at the past can contribute to a better understanding of the present in the field of science too, we discuss here two aspects of the relationship between early 20th century anatomic pathology and psychiatry that have received very little attention, in Italy at least. There was much debate between these two disciplines throughout the 19th century, which began to lose momentum in the early years of the 20th, with the arrival on the scene of schizophrenia (a disease histologically sine materia) in all its epidemiological relevance.The First World War also contributed to the separation between psychiatry and pathology, which unfolded in the fruitless attempts to identify a histopathological justification for the psychological trauma known as shell shock. This condition was defined at the time as a "strange disorder" with very spectacular symptoms (memory loss, trembling, hallucinations, blindness with no apparent organic cause, dysesthesias, myoclonus, bizarre postures, hemiplegia, and more), that may have found neuropathological grounds only some hundred years later.Among the doctors with a passed involvement in the conflict, Ugo Cerletti, the inventor of electroshock treatment, focused on the problem of schizophrenia without abandoning his efforts to identify its organic factors: if inducing a controlled electric shock, just like an experimentally-induced epileptic seizure, seems to allay the psychotic symptoms and heal the patient, then what happens inside the brain? In seeking histological proof of the clinical effects of electroconvulsive therapy ("the destruction of the pathological synapses"), and attempting to isolate molecules (that he called acroagonins) he believed to be synthesized by neurons exposed to strong electric stimulation, Cerletti extended a hand towards anatomic pathology, and took the first steps towards a neurochemical perspective. However his dedication to finding a microscopic explanation for schizophrenia - in the name of a "somatist" approach that, some years earlier, the psychiatrist Enrico Morselli had labelled "histomania" - was unable to prevent psychiatry from moving further and further away from anatomic pathology.

Enrico Sertoli and the supporting cells of the testis "Morphology is function".

In 1865, Enrico Sertoli, at the age of 23, published an article in his own name entitled: "About the existence of special branched cells in the seminiferous tubules of the human testis". These were Sertoli's ideal cells; in this paper he arrived at a perspicacious description of the morphology and function of these cells and in the subsequent articles he investigated the topic of spermatogenesis. Despite the importance of Sertoli's discovery, the attention of the scientific literature remained very limited after Sertoli's death for half a century and the partial eclipse finished only in the 1970s of the twentieth century.

Pathologica in the time of "Spanish flu".

The pandemic "Spanish flu", that in a few weeks of the autumn 1918 caused in Italy a number of deaths between 350.000 and 600.000, was widely discussed by the scientific community, although very little of that debate leaked out, because of the military censorship.In the present article we comment on the original papers describing the hemorrhagic pneumonia, and on discussions about the ideas of the origin of the pandemic infection (Pfeiffer bacillus, vs streptococcus or other bacteria vs a "viral hypotesis") that occurred in Pathologica during and soon after that ominous pandemia.

Quality of life in long-term survivors treated for metastatic medulloblastoma with a hyperfractionated accelerated radiotherapy (HART) strategy.

PURPOSE: An intensive therapeutic strategy for metastatic medulloblastoma was launched in 1998 in our Institution. The aim of this study was to examine the long-term quality of life (QoL) in survivor patients at least 3 years after the end of the treatment. METHODS: Patients were asked to complete self-administered QoL questionnaires. An index of physical impairment (IPI) was scored (range 0-100; the lower the score the better) based on clinical objective observations. Patients were divided into two groups (lower IPI group, and higher IPI group) and descriptively compared accordingly. RESULTS: The study was completed by 25/33 eligible patients. Despite patients with a higher IPI reported worse perceived health condition, they had better emotional and psychological scores than those with a lower IPI in all QoL questionnaires. CONCLUSION: In our sample, patients with more severe objective and perceived physical impairments reported a better psychosocial QoL, possibly because the greater attention paid to them by society and family contributes to a better adjustment in long-term survivors. On this base, it should be recommended that all survivors receive a strong support as the most impaired patients.

Dying after cure: A case of suicide in an adolescent treated for cancer.

Although suicide among childhood cancer survivors is rare, there is still a significantly higher risk in this population than in healthy adolescents. A 17-year-old girl cured of Burkitt lymphoma committed suicide after completing her treatment. She had never previously shown signs of psychological suffering and was in good general health. This case made the operators wonder how this tragic possibility might be prevented. It is essential for the ongoing monitoring of the psychological and social suffering of young people during follow-up programs to be assured by a multidisciplinary team involved in the patient's global care.

Airway cell involvement in intermittent hypoxia-induced airway inflammation.

PURPOSE: Respiratory inflammation has been described in patients with obstructive sleep apnea syndrome, but it is unknown whether the increased neutrophil and interleukin (IL)-8 levels observed in induced sputum reflect systemic or local airway inflammation. We assessed the potential role of resident cells in intermittent hypoxia-induced airway inflammation. METHODS: Airway epithelial cells (AEC) and bronchial smooth muscle cells (BSMC) were exposed to intermittent hypoxia (IH) in vitro. Cell supernatants were assessed for matrix metalloproteinase, growth factor, and cytokine expression. The role of IH on neutrophil and BSMC migration capacities was evaluated, and the effect of supernatants from IH-exposed or control AEC was tested. RESULTS: Compared to normoxic conditions, 24 h of exposure to IH induced a significant increase of MMP-9 and MMP-2 expression and pro-MMP-9 activation (p < 0.05), and IL-8 (p < 0.05), platelet-derived growth factor (PDGF)-AA (p < 0.05), and vascular endothelial growth factor (VEGF) (p < 0.05) expression by AEC and VEGF expression (p = 0.04) by BSMC. Neutrophil chemotaxis and BSMC migration were enhanced by IH and supernatants of IH-exposed AEC (112.00 ± 4.80 versus 0.69 ± 0.43 %, p = 0.0053 and 247 ± 76 versus 21 ± 23, p = 0.009 respectively). This enhanced BSMC migration was totally abolished in the presence of an antibody blocking PDGF-AA. CONCLUSIONS: These data suggest a specific inflammatory response of airway cells to IH, independently of systemic events.

[Psycho-organic diseases in children and adolescents affected by pediatric neoplasms]. / Disturbi psico-organici in bambini e adolescenti affetti da neoplasie pediatriche.

At Pediatric Oncology Centers, psychological intervention and psychotherapy are generally offered to children and adolescents for supporting their adjustment to disease and treatment. The clinical practice, however, point out that cognitive and emotional symptoms, such as psychic distortions, fatigue, anxiety, irritability and depression, are sustained by biological mechanisms connected with disease and treatment and not respondent to psychological consultation and to other psychosocial resources. These manifestations could interfere with treatment or with the long-term adjustment and call for psychopharmacological treatments. Biological factors able to cause these alterations are not yet studied in depth in clinical tradition and scientific literature on the integration of psychological and psychopharmacological intervention in pediatric oncology is still poor. In this paper organic components of psychic and behavioral alterations in the course of disease are illustrated, considering the symptoms, causes and possible remedies in the light of the most recent interdisciplinary views. The main mechanism connected with oncologic treatments - chemotherapy, surgery, radiotherapy - and responsible for psycho-organic alterations in children and adolescent with cancer are also described.

A patient with meningeal melanomatosis treated for periodontal disease with a bone regeneration procedure and dental implants: clinical and behavioral management to support medical compliance.

BACKGROUND: During the last three decades dental implants have become increasingly used in partially edentulous periodontally compromised patients. The type of bacteria in the peri-implant sulcus is influenced by the periodontal bacteria present on the surfaces of the remaining teeth. Peri-implant sulci of partially edentulous individuals harbour more motile rods and spirochetes than those of fully edentulous individuals. If Peri-implantitis arises, it may lead to implant failure. This complication occurs more frequently in patients with poor oral hygiene. This is a site-specific bacterial infection similar to that caused by periodontal bacteria around teeth and it should be prevented. AIM: This study was conducted to radiographically evaluate hard tissue response around 6 implants, over a 2-year period, in a previously surgically treated patient affected by severe chronic periodontitis. Psychological considerations and behavioral management of the patient are described. MATERIALS AND METHODS: A complex implant-perio-prosthodontic case of a 54-year-old man affected by meningeal melanomatosis with a history of generalized severe chronic periodontitis was recruited. A comprehensive periodontal examination around teeth was accomplished before periodontal and implant treatment. After diagnostic work-up, compromised teeth from 1.3 to 2.3 and from 3.2 to 4.2 were extracted. Tooth 1.7 was also extracted. Afterwards fixed provisional restoration rehabilitated all the natural dentition and the missing teeth. Endodonthic therapies were conducted on all the teeth due to high dentinal sensitivity and pre-prosthodontic crown reconstructions performed. Periodontal surgery with modified Widman flaps were then accomplished on all the teeth. Three months later four maxillary implants in position 1.3,1.1,2.1,2.3 and two mandibular implants in position 4.2,3.2 were inserted. During mandibular implants positioning, the mental mussels were isolated and detached to achieve proper guided bone regeneration. During implant surgery, due to systemic conditions concern, the patient underwent intravenous sedation. Five months later the implants and the teeth were rehabilitated with fixed metal-ceramic bridges. Regarding the upper prosthetic rehabilitation, the incisors marginal edges were kept vertical to the nasal spine, due to lack of previous reference points. According to the reference points previously determined, the difference in bone level between radiographs taken at implants insertion and at the maintenance appointments was calculated. RESULTS: The health of the periodontally treated teeth resulted greatly enhanced. The mean alveolar bore loss was 0,30 mm after a 2-year observation period. CONCLUSIONS: The control of the periodontal disease before implant insertion in patients with severe chronic periodontitis is of paramount importance, as well as a regular maintenance program is essential for the health of the periodontal and peri-implant tissues. The management of patients with complex needs requires a multidisciplinary team designed to meet all the patient's needs on various levels.

Evaluación del conocimiento de los padres de la técnica de aerosolterapia con aerocámara / Evaluation of parental knowledge of the aerosol technique with holding chamber

Introducción. Los episodios de tos, disnea y sibilancias son causa frecuente de consulta pediátrica. Su tratamiento de elección es la administración de fármacos a través de la aerosolterapia. El éxito de esta estrategia depende de la correcta aplicación de la técnica inhalatoria. Objetivo. Evaluar el conocimiento de padres de niños con patología obstructiva recurrente de la vía aérea en el uso de la aerosolterapia con aerocámara. Población y métodos. Estudio transversal, observacional, descriptivo. Se incluyeron aleatoriamente padres de niños menores de 6 años con tos, disnea y/o sibilancias con antecedentes de uso de aerocámara en la consulta al Servicio de Pediatría y/o de Alergia e Inmunología. Se evaluó el conocimiento en el empleo del inhalador mediante observación de la técnica. Resultados. Se incluyeron 114 niños, 51% masculino, con una edad promedio de 29,23 meses (DE=18,30). La persona a cargo de realizar la aerosolterapia tenía una media de edad de 32,28 años (DE=5,29); la mayoría de los responsables evaluados fueron madres (92,98%), con nivel de educación superior (71,05%). La forma de aprendizaje de la técnica fue demostrativa visual en 62 casos (54,4%), y el principal instructor de la misma fue el pediatra. Se demostró que 68 (72%) padres no realizaban en forma correcta la técnica y se encontró asociación entre edad del paciente y la correcta realización de la aerosolterapia (r=0,21; p=0,03). Conclusión. La mayoría de los padres realizan la aerosolterapia de forma incorrecta y la edad del niño influye en la técnica de la terapia inhalatoria.(AU)

Introduction. Symptoms of cough, dyspnea and wheezing are common cause for medical consultation. Their treatment is the administration of drugs through the aerosol. The success of this strategy depends on the correct application of inhalation technique. Objective. To evaluate the knowledge of parents of children with recurrent obstructive airway disease in the use of aerosol therapy with valved holding chamber. Population and Methods. Cross-sectional, observational, descriptive study. Randomly included parents of children under six years with cough, dyspnea and / or wheezing with a background of use in the office holding chamber of Pediatric and / or of Allergy and Immunology section of an Hospital. We evaluated the knowledge about the inhaler technique by medical observation. Results. We included 114 children, 51% male, with an average age of 29.23 months (SD=18.30). The median age o the caregiver responsible for conducting the aerosol therapy was 32.28 years (SD=5.29); the majority of evaluated makers were mothers (92.98%) with higher education level (71.05%). The most frequent way for learning was the visual demonstration technique in 62 cases (54.4%), and the main instructor was the pediatrician. Sixty-eight (72%) of parents did not perform properly the inhalation technique and a positive association was found between patient age and the proper realization of the aerosol (r=0.21; P=0.03). Conclusion. Most parents perform incorrectly aerosol therapy with valved holding chamber and the child's age influences the inhalation technique.(AU)

[Firearms related suicide/homicide rate among the security guards population in Italy]. / Suicidi e omicidi con l'arma di ordinanza. Analisi della casistica nelle guardie particolari giurate in Italia.

OBJECTIVE: The main aim of this study is evaluating the suicide/homicide rate of the Italian security guards population compared to other armed and general populations during a recent period. METHODS: The authors reviewed the incidence of suicides and homicides among security guards from 1996 to 2006 and, where information was available, a comparison was made with Italian population adapted by age. Comparisons with the general population were also made. RESULTS: The average rate of firearms related suicide among the security guards population during the established period was 11.7 per 100,000 persons-years (95% CI = 6.6-16.7) compared to a guns-related suicide rate of 0.7 per 100,000 person-years, (95% CI = 0.6-0.7) and a non-guns related rate of 5.5 per 100,000 persons-years, (95% CI = 5.2-5.9) for the general population adjusted for age. The overall homicide rate among security guards during the period was 11.4 per 100,000 person-years (95% CI = 6.2-15.4) compared with the homicide rate for the Italian population of 5.4 per 100,000 persons-years, (95% CI = 7.3-15.4). CONCLUSION: The rate of suicide and homicide among the Italian security guards population was higher than the suicide/homicide rate in the general population. These results show that the phenomenon we have described needs attention and specific prevention activities.

Water load test before and after PPI therapy in patients with gastro-oesophageal reflux disease.

BACKGROUND: Patients with gastro-oesophageal reflux disease may complain of epigastric pain, bloating, early satiety, epigastric fullness, epigastric burning, nausea and vomiting. AIMS: To evaluate the symptoms in response to gastric distension and its relationship to a therapeutic course in patients with gastro-oesophageal reflux disease using the water load test, compared to healthy controls. METHODS: Thirty gastro-oesophageal reflux disease patients with grade A oesophagitis (studied before and after 4 weeks of therapy with esomeprazole, 40 mg per day) and 15 patients with reflux-related symptoms demonstrated at wireless pH monitoring (non-erosive reflux disease) were compared to 30 healthy volunteers. RESULTS: Patients with grade A oesophagitis and with reflux-related symptoms ingested significantly lower water volumes than did controls, before onset of fullness, without statistically significant difference between erosive or non-erosive gastro-oesophageal reflux disease; this variable improved in patients after treatment. Nausea scores were higher basally in patients, pre- and post-therapy, and improved after therapy. Thirty-minute fullness and bloating scores improved after therapy in all gastro-oesophageal reflux disease patients compared to controls and pre-therapy. In all pre-treatment patients, a significant correlation was found only with epigastric fullness; after treatment, there was no significant relationship between the water load and the symptom scores. CONCLUSIONS: In patients with reflux-related symptoms, with or without grade A oesophagitis, the water load test is frequently abnormal, suggesting an altered gastric function. This could explain the incomplete resolution of symptoms after treatment in some patients, and should lead to additional studies aimed at exploring gastric function in gastro-oesophageal reflux disease patients.

Phenomenology and emotional impact of neuropsychiatric symptoms in orthotopic liver transplant for hepatocellular carcinoma.

BACKGROUND: Few studies have focused on neuropsychiatric symptoms like hallucinations or delusions occurring in the early posttransplant period. The aim of this study was to estimate the percentage of patients reporting neuropsychiatric symptoms in the immediate postoperative phase, to describe the phenomenology, and to evaluate the emotional impact of such disorders. METHOD: We studied 94 consecutive patients who underwent orthotopic liver transplant (OLT) for hepatocellular carcinoma at least 30 days prior. The presence of neuropsychiatric symptoms were retrospectively evaluated through a semistructured interview. RESULTS: Overall 49 patients (52%) reported various postoperative neuropsychiatric symptoms. None of the demographic and clinical variables showed significant associations, except for barbiturate administration; patients using barbiturates showed a lower percentage of neuropsychiatric symptoms. It was a time-limited phenomenon that in most cases resolved by day 7 after transplantation. Interestingly, the most frequent emotion perceived was surprise and not fear; a nontrivial amount of patients reported happiness, while many patients reported no emotion. CONCLUSIONS: The results of this study suggested the usefulness of a registry of the neurological and psychiatric complications after OLT that may help to clarify the pathogenic mechanisms of such complications and implement uniform protocols of prevention and treatment. In fact, better knowledge of the phenomenology of neuropsychiatric symptoms in OLT recipients could allow easier symptom recognition and therapy adjustments on the basis of the emotional impact of such symptoms on patients, family, and caregivers, as well as increase patients' awareness and capability to face this experience.

Colon and gastric metastases from a primary signet-ring cell carcinoma of the urinary bladder.

Signet-ring cell carcinoma is a relatively rare neoplasm that rarely occurs in the urinary bladder. We report a case of a 60-year-old man who presented with gross haematuria. Cystoscopy revealed a white sessile tumour of the anterior bladder wall. The histological diagnosis showed a primary signet-ring cell carcinoma of the bladder (T3bN0M0). Eighteen months after radical cystectomy, the patient developed colon and stomach metastases. This case represents the first description of a primary signet-ring cell carcinoma of the urinary bladder with gastrointestinal metastases.

Nutritional state and energy balance in cirrhotic patients with or without hypermetabolism. Multicentre prospective study by the 'Nutritional Problems in Gastroenterology' Section of the Italian Society of Gastroenterology (SIGE).

BACKGROUND AND AIMS: A total of 334 stable, compensated cirrhotic patients admitted to 10 Italian Gastroenterology Units were included in a prospective study to evaluate nutritional state and energy balance in liver cirrhosis. MATERIALS AND METHODS: Nutritional state and calorie intake were examined in the total population, while adequacy of calorie intake versus measured total energy expenditure was evaluated in a comparable subpopulation and in 40 matched controls, by computing the energy balance. RESULTS: Our data demonstrated that: (i) malnutrition was present in 25% of the total patients and significantly correlated with the Child's group (A=16%; B=25%; C=44%); (ii) the type of malnutrition is influenced by mBEE: normometabolic patients exhibit a significant (p<0.005) reduction of mid-arm fat area while both hypermetabolic and hypometabolic patients show a significant (p<0.005) decline in kg of free fat mass; (iii) normometabolic and hypometabolic patients have a negative energy balance, due to a high level of physical activity (127+/-14 kJ) in the first group and a reduced energy intake/kg body weight (102+/-12 kJ) in the second; (iv) hypermetabolic patients have a positive energy balance due to decreased daily physical activity/kg body weight (108+/-28 kJ); (v) malnourished and normometabolic patients eat a significantly (p<0.05) reduced percentage of protein whereas malnourished and hypermetabolic patients eat a significantly increased percentage of fat (p<0.05). CONCLUSION: Although multivariate regression analysis confirms that the Child-Pugh's score is a better independent predictor of malnutrition, the measure of REE, TEE, calorie intake and energy balance need to be routinely performed in cirrhotic patients, in order to recognise hypermetabolic and hypometabolic patients (approximately 30%) in whom the nutritional and metabolic parameters are indispensable as a basis for designing and prescribing personalised nutritional strategies that can treat muscle malnutrition and thus improve the morbidity and mortality rates.

Hypoxia reduces alveolar epithelial sodium and fluid transport in rats: reversal by beta-adrenergic agonist treatment.

In cultured alveolar epithelial cells, hypoxia induces a downregulation of the two main Na proteins, the epithelial Na channel (ENaC) and the Na,K-ATPase. However, the in vivo effects of hypoxia on alveolar epithelial transport have not been well studied. Therefore, the objectives of this study were to investigate in an in vivo rat model if hypoxia induces a reduction in vectorial Na and fluid transport across the alveolar epithelium in vivo, and if a change in net fluid transport is associated with modification in the expression and/or activity of Na transport proteins. Rats were exposed to 8% O(2) from 3 to 24 h. Hypoxia induced a progressive decrease in alveolar liquid clearance (ALC) reaching 50% at 24 h, an effect that was related primarily to a decrease in amiloride-sensitive transepithelial Na transport. On RNase protection assay of alveolar type II (ATII) cells isolated immediately after hypoxic exposure, steady state levels of mRNA were increased for alpha-rENaC and beta(1)-Na, K-ATPase, whereas the levels of gamma-rENaC and alpha(1)-Na,K-ATPase were unchanged. On Western blots of ATII cell membranes, alpha-ENaC subunit protein slightly increased, whereas the amount of alpha(1)- and beta(1)-Na,K-ATPase protein were unchanged with hypoxia. Thus, the decrease in transepithelial Na transport was not explained by a parallel change in gene expression or the quantity of transport proteins. Interestingly, hypoxia-induced decrease in ALC was completely reversed by intra-alveolar administration of the beta(2) agonist, terbutaline (10(-4) M). These results suggest that hypoxia-induced decrease in Na transport is not simply related to a downregulation of Na transport proteins but rather to a decrease in Na protein activity by either internalization of the proteins and/or direct alteration of the protein in the membrane. The dramatic increase of ALC with beta(2)-agonist therapy indicates that the decrease of transepithelial Na and fluid transport during hypoxia is rapidly reversible, a finding of major clinical significance.

Hypoxia regulates gene expression of alveolar epithelial transport proteins.

Alveolar hypoxia occurs during ascent to high altitude but is also commonly observed in many acute and chronic pulmonary disorders. The alveolar epithelium is directly exposed to decreases in O(2) tension, but a few studies have evaluated the effects of hypoxia on alveolar cell function. The alveolar epithelium consists of two cell types: large, flat, squamous alveolar type I and cuboidal type II (ATII). ATII cells are more numerous and have a number of critical functions, including transporting ions and substrates required for many physiological processes. ATII cells express 1) membrane proteins used for supplying substrates required for cell metabolism and 2) ion transport proteins such as Na(+) channels and Na(+)-K(+)-ATPase, which are involved in the vectorial transport of Na(+) from the alveolar to interstitial spaces and therefore drive the resorption of alveolar fluid. This brief review focuses on gene expression regulation of glucose transporters and Na(+) transport proteins by hypoxia in alveolar epithelial cells. Cells exposed to severe hypoxia (0% or 3% O(2)) for 24 h upregulate the activity and expression of the glucose transporter GLUT-1, resulting in preservation of ATP content. Hypoxia-induced increases in GLUT-1 mRNA levels are due to O(2) deprivation and inhibition of oxidative phosphorylation. This regulation occurs at the transcriptional level through activation of a hypoxia-inducible factor. In contrast, hypoxia downregulates expression and activity of Na(+) channels and Na(+)-K(+)-ATPase in cultured alveolar epithelial cells. Hypoxia induces time- and concentration-dependent decreases of alpha-, beta-, and gamma-subunits of epithelial Na(+) channel mRNA and beta(1)- and alpha(1)-subunits of Na(+)-K(+)-ATPase, effects that are completely reversed after reoxygenation. The mechanisms by which O(2) deprivation regulates gene expression of Na(+) transport proteins are not fully elucidated but likely involve the redox status of the cell. Thus hypoxia regulates gene expression of transport proteins in cultured alveolar epithelial type II cells differently, preserving ATP content.

[Psychological assistance in organ transplantation]. / L'assistenza psicologica nei trapianti d'organo.

The aim of this report is introducing with a series of psychological, psychiatric and psychosocial problems, that can arise, at every point, in the procedure of organ transplantations. Different areas of intervention are considered: the assistance to the patients and their families during the pre- and post-operative periods; the evaluation of transplant recipients' quality of life; ethical and psychological problems of living kidney donation; psychosocial support to donors' families; the training of the intensive therapy units to entertain relationships with donors' relatives; the delicate psychological aspects of transplantation during childhood. The sense of awareness about these matters is growing in Italy too, and many initiatives of psychological and psychiatric help are being developed in collaboration with several transplantation centres.

Hypoxia increases glyceraldehyde-3-phosphate dehydrogenase transcription in rat alveolar epithelial cells.

Alveolar epithelial type II (ATII) cells are particularly hypoxia-tolerant in vitro. As one of the mechanisms of hypoxia tolerance is the induction of certain proteins, one of which is glyceraldehyde-3-phosphate dehydrogenase (GAPDH), we investigated whether hypoxia modified GAPDH expression in ATII cells. Hypoxia induced a time- and O(2) concentration-dependent accumulation of GAPDH mRNA in cultured rat ATII cells (2- to 3-fold the normoxic value after 18 h in 0% O(2)), an effect completely reversed by reoxygenation. GAPDH mRNA induction was accounted for by an increase in GAPDH gene transcription during hypoxia with no change in mRNA stability. GAPDH protein synthesis increased 3- to 4-fold after 18 h of 0% O(2), while the GAPDH protein steady-state level rose by 75%. GAPDH enzymatic activity in hypoxic cell homogenates increased by 45%. These results indicate that hypoxia induces GAPDH expression in ATII cells through an increase in transcription.

Airway obstruction in bronchial sarcoidosis: outcome with treatment.

STUDY OBJECTIVE: Airway obstruction (AO) in sarcoidosis is reported to be associated with respiratory symptoms, increased morbidity, and an increased mortality risk. Because AO in sarcoidosis may result from several causes, the therapeutic benefit of corticosteroids is difficult to determine. The aim of this study was to evaluate the therapeutic response of AO attributable to sarcoid granulomas in the bronchial wall. PATIENTS: We selected 11 patients who had sarcoidosis with AO (defined as FEV(1)/vital capacity [VC] < 70%) associated with sarcoid granulomas on an endobronchial biopsy. Exclusion criteria were history of asthma, smoker or ex-smoker, stage 4 disease, evidence of extrinsic compression by enlarged lymph nodes, and localized endobronchial stenosis seen during fiberoptic bronchoscopy. INTERVENTIONS: We compared the results of pulmonary function tests and clinical, radiologic, and biological findings at baseline with those obtained at the time of the last pulmonary function tests available, between the sixth and 12th months of treatment. Eight patients took oral corticosteroids (20 to 60 mg/d initially), one received IV methylprednisolone pulses, another took oral hydroxychloroquine, and the last one received IM methotrexate. MEASUREMENTS AND RESULTS: With treatment, FEV(1) and FEV(1)/VC significantly improved in eight patients (72%), normalized in four patients, and was unchanged in the remaining three patients. The mean FEV(1) increased from 60.8 +/- 10.8% to 76 +/- 13.7% of the predicted value (p < 0.02). VC did not change significantly. FEV(1)/VC increased from 76.1 +/- 6.4% to 87.6 +/- 10.7% of the predicted value (p < 0.01). Dyspnea on exertion and other clinical findings were attenuated in 10 patients; the chest radiograph improved in 9 patients, and normalized in 5 patients. The mean serum angiotensin-converting enzyme level decreased from 112 +/- 48 to 58 +/- 40 IU/mL (p < 0.05), and normalized in four patients. CONCLUSION: The present study indicates that AO caused by sarcoid granulomas in the bronchial wall can be either partially or completely reversed by treatment with a concomitant attenuation of pulmonary symptoms.