Preoxygenation of different preservation solutions for porcine pancreas preservation.

INTRODUCTION: Organ preservation quality impacts porcine islet cell isolation and transplantation success. Among several preservation methods, the two-layer method is promising, but technically demanding and fails to deliver sufficient oxygen. The use of hyperbaric oxygenation may be an easier, more effective method to supply high partial pressure of oxygen (pO(2)) for organ storage. Therefore, the aim of this study was to test the capability of preoxygenation of various preservation solutions with HBO to maintain high pO(2) levels. METHODS: University of Wisconsin (UW), Custodiol, Perfadex, or Celsior solutions were preoxygenated in a pressure chamber. NaCl served as the control. pO(2) levels were measured at defined times. The oxygen storage capability was evaluated by leaving the storage bottles open for 2 minutes. RESULTS: It was feasible to preoxygenate preservation solutions. The best solution to maintain high pO(2) tensions was Perfadex, followed by Celsior, and UW. DISCUSSION: The greater the amount of oxygen in the preservation solution, the more oxygen can be delivered to the preserved pancreas. Further studies on the influence of preoxygenated preservation solutions on the porcine pancreas are warranted to improve organ quality, porcine islet cell isolation, and transplantation success.

Arterial oxygen tension increase 2-3 h after hyperbaric oxygen therapy: a prospective observational study.

BACKGROUND: Inhalation of hyperbaric oxygen (HBO) has been reported to decrease arterial oxygen tension (PaO(2)) in the early period after exposure. The current investigation aimed at evaluating whether and to what extent arterial blood gases were affected in mechanically ventilated intensive care patients within 6 h after HBO treatment. METHODS: Arterial blood gases were measured in 11 ventilated subjects [nine males, two females, synchronized intermittent mandatory ventilation (SIMV) mode] undergoing HBO therapy for necrotizing soft tissue infection (seven patients), burn injury (two patients), crush injury (one patient) and major abdominal surgery (one patient). Blood gases were obtained with the patients in the supine position under continuous analgesia and sedation before the hyperbaric session (baseline), during isopression, after decompression, after each transport, and 1, 2, 3 and 6 h after exposure. Heart rates and blood pressures were recorded. Intensive care unit (ICU) ventilator settings remained unchanged. Transport and chamber ventilator settings were adjusted to baseline with maintenance of tidal volumes and positive end-expiratory pressure (PEEP) levels. The hyperbaric protocol consisted of 222.9 kPa (2.2 absolute atmospheres) and a 50-min isopression phase. The paired Wilcoxon's test was used. RESULTS: Major findings (median values, 25%/75% quartiles) as per cent change of baseline: PaO(2) values decreased by 19.7% (7.0/31.7, P < 0.01) after 1 h and were elevated over baseline by 9.3% (1.5/13.7, P < 0.05) after 3 h. SaO(2), alveolar-arterial oxygen tension difference and PaO(2)/FiO(2) ratio behaved concomitantly. Acid-base status and carbon dioxide tension were unaffected. CONCLUSION: Arterial oxygen tension declines transiently after HBO and subsequently improves over baseline in intensive care patients on volume-controlled mechanical ventilation. The effectiveness of other ventilation modes or a standardized recruitment manoeuvre has yet to be evaluated.

Hyperbaric oxygen in tinnitus: influence of psychological factors on treatment results?

INTRODUCTION: The standard treatment of subjective tinnitus hardly reaches the level of placebo controls. Though the effectiveness of hyperbaric oxygenation (HBO) for subjective tinnitus has never been objectified, it is still advocated by some institutions. We analyzed the effectiveness of hyperbaric oxygen treatment in the context of accompanying factors. PATIENTS AND METHODS: We randomized 360 patients suffering from tinnitus into 2 HBO treatment protocols (group A: 2.2 bar for 60 min bottom time and group B: 2.5 bar for 60 min bottom time once a day for 15 days). All patients were asked to fill in a questionnaire (social and medical history, tinnitus characteristics, pre-HBO duration of tinnitus, prior therapy, pretreatment expectation, accompanying symptoms). A subjective assessment of the therapeutic effect was obtained. RESULTS: Twelve patients (3.3%) experienced complete remission of tinnitus, in 122 (33.9) the intensity lessened, and 44 (12.2%) had a subjectively agreeable change of noise characteristics. No change was found in 157 cases (43.6%) and 25 (6.9%) experienced deterioration. There was no statistically significant difference between groups A and B (p > 0.05). Out of 68 patients with a positive expectation of HBO effects, 60.3% stated that the tinnitus had improved whereas only 47.2 and 19%, respectively, out of patients who underwent therapy with an indifferent (n = 271) or negative expectation (n = 21) reported an improvement. The influence of subjective expectation on the outcome was statistically significant (p < 0.05). CONCLUSION: The therapeutic effects of HBO on subjective tinnitus may be substantially influenced by psychological mechanisms.

Hyperbaric oxygen (HBO2) in tinnitus: influence of psychological factors on treatment results?

UNLABELLED: HBO2 for subjective tinnitus has never been objectified, yet it is still advocated by many institutions. We analyzed the therapeutic effect of HBO2 treatment in the context of accompanying factors, especially focusing on the patients' attitude towards HBO2 prior to therapy. METHODS: 360 patients suffering from tinnitus were investigated in this study. They were randomized into 2 hyperbaric treatment protocols, one at 2.2, the other at 2.5 bar, 60 min bottom time each. All patients were asked to fill in a questionnaire (social and medical history, tinnitus characteristics, pre-HBO2 duration oftinnitus, prior therapy, pre-treatment expectation, accompanying symptoms) immediately before and one month after HBO2 treatment. The subjective impact of tinnitus on daily life was assessed using a score from 1 to 10 prior to HBO2 and one month after the treatment. RESULTS: 12 patients (3.3%) experienced complete remission of tinnitus, in 122 (33.9%) the intensity lessened, and 44 (12.2%) had a subjectively agreeable change of noise characteristics. 157 (43.6%) stated no change and 25 (6.9%) experienced deterioration. There was no statistically significant difference between the two hyperbaric protocols (p > 0.05). Out of 68 patients with positive expectation towards HBO2 therapy 60.3% stated that the tinnitus had improved whereas out of the patients who underwent therapy with indifferent (N = 271) or negative expectations (N = 21) only 47.2% and 19%, respectively, reported an improvement. The influence of both positive and negative anticipation on the outcome was statistically significant (p < 0.05). CONCLUSION: The therapeutic effects of HBO2 on subjective tinnitus might be greatly due to psychological mechanisms triggered by the attitude of the patient towards HBO2 therapy prior to the treatment.

Necrotizing sarcoid granulomatosis--is it different from nodular sarcoidosis?

BACKGROUND: Necrotizing sarcoid granulomatosis (NSG) was initially defined as a granulomatosis with features in between sarcoidosis and Wegener's granulomatosis (WG), but without extrapulmonary involvement. Subsequent reports have shown that extrapulmonary involvement does exist, and some have suggested NSG as a variant of sarcoidosis. MATERIAL AND METHODS: We studied 10 cases from 3 institutions, and compared clinical and histologic features with those of nodular sarcoidosis and WG. We have analyzed the 10 cases for mycobacterial chaperonin and for the insertion sequence 6110 by PCR. RESULTS AND CONCLUSIONS: Nodular aggregates of granulomas in NSG were similar to those seen in nodular sarcoidosis. Granulocytic vasculitis, a hallmark of WG was not seen in any of the NSG cases. Granulomatous vasculitis was a common feature in cases of NSG, and did not differ from that seen in sarcoidosis. The only unique feature of NSG is infarct-like necrosis, induced by the vasculitis, which might also be interpreted as a function of the duration of the vasculitis, leading ultimately to vascular obstruction. NSG based on our morphologic findings is best classified as a variant of nodular sarcoidosis. In contrast to our findings in sarcoidosis mycobacterial DNA was not found in any of the 10 cases.

Hemodynamic and oxygenation profiles in the early period after hyperbaric oxygen therapy: an observational study of intensive-care patients.

BACKGROUND: We studied whether hemodynamic and oxygenation profiles are altered in critically ill patients after exposure to hyperbaric oxygen (HBO). METHODS: Ten intensive-care patients (two females, eight males) undergoing HBO treatment after major abdominal surgery, after burn injury and after CO poisoning were included. All subjects were put on mechanical ventilation and received continuous sedation, and had HBO treatment at 2.2 absolute atmospheres for 50 min. DESIGN: Observational prospective study, and repeated measure design. RESULTS: Hemodynamic and oxygen transport patterns were determined before (C0), 1 h (C1) and 2 h (C2) after HBO therapy with continuous cardiac output dual oximetry pulmonary arterial catheter, a central venous and radial arterial line. Data were analyzed with non-parametric repeated measure analysis. Key results are expressed as a percentage of baseline (C0 values correspond to 100%) at C1 and C2 (median values, lower and upper limit of confidence interval): cardiac index [C1: 105% (98-135), C2: 99% (91-117), P = 0.19], systemic (P = 0.62) and pulmonary vascular (P = 0.76) resistance indices were unchanged, but pulmonary venous admixture (Qs/Qt) increased [C1: 173% (112-298), C2: 140% (92-241), P = 0.00002)] and arterial oxygen tension decreased [C1: 76% (67-94), C2: 82% (72-112), P = 0.010]. CONCLUSION: The hemodynamic profile remained unaffected. The increase in Qs/Qt and the decrease in PaO2 may be attributed to the inhalation of HBO, and both are reversible.

Hyperbaric oxygen--an effective tool to treat radiation morbidity in prostate cancer.

PURPOSE: We report the results of hyperbaric oxygen therapy (HBO) used in the treatment of radiation cystitis and proctitis following irradiation of prostate cancer. MATERIALS AND METHODS: Between June 1995 and March 2000, 18 men (median age 71 years) with radiation proctitis (n=7), cystitis (n=8), and combined proctitis/cystitis (n=3) underwent HBO therapy in a multiplace chamber for a median of 26 sessions (range 2-60). The treatment schedule (2.2-2.4 atmospheres absolute, 60 min bottom time, once-a-day, 7 days a week) was set at a lower limit of 20 sessions; the upper limit was left open to symptom-related adjustment. Prior to HBO treatment, RTOG/EORTC late genitourinal (GU) morbidity was Grade 2 (n=3), Grade 3 (n=6) or Grade 4 (n=2); modified RTOG/EORTC late gastrointestinal (GI) morbidity was either Grade 2 (n=4) or Grade 3 (n=6). RESULTS: Sixteen patients underwent an adequate number of sessions. RTOG/EORTC late GU as well as modified GI morbidity scores showed a significant improvement after HBO (GI, P=0.004; GU, P=0.004; exact Wilcoxon signed rank test); bleeding ceased in five out of five patients with proctitis and in six out of eight patients with cystitis; one of those two patients, in whom an ineffective treatment outcome was obtained, went on to have a cystectomy. CONCLUSIONS: HBO treatment seems to be an effective tool to treat those patients with late GI and GU morbidity when conventional treatment has led to unsatisfactory results. Particularly in patients with radiation cystitis, HBO should not be delayed too long, as in the case of extensive bladder shrinkage improvement is hard to achieve.

Loss of heterozygosity on chromosome arm 11q in lung carcinoids.

Neuroendocrine lung tumors such as typical carcinoid, atypical carcinoid, small-cell lung carcinoma, and large-cell neuroendocrine carcinoma represent a variable group with different biologic characteristics and unclear genetical relationships. We investigated the pattern of allelic loss on chromosome arm 11q in 20 sporadic carcinoid tumors of the lung using 10 microsatellite markers. Loss of heterozygosity was found in 13 of 20 tumors. In 5 of 9 typical carcinoids, 3 distinct regions of allelic loss were identified: 11q13.1 (D11S1883), 11q14.3-11q21 (D11S906), and 11q25 (D11S910). Atypical carcinoids showed loss of heterozygosity at 4 different regions: the first, most proximal region at 11q13 between markers PYGM and D11S937; the second at 11q14.3-11q21 (D11S906); and the third and fourth defined by markers D11S939 (11q23.2-23.3) and D11S910 (11q25). However, the region 11q13 harboring the MEN1 gene was more frequently affected in atypical carcinoids (7 of 11) than in typical carcinoids (2 of 9). The high rate of allelic losses within chromosomal region 11q13 in atypical carcinoids emphasizes the importance of this region for tumor development. We also recognized that more aggressive atypical carcinoids defined by high mitotic counts, vascular invasion, and/or organ metastasis are combined with increased allelic losses. HUM PATHOL 32:333-338.

Review of severe osteoradionecrosis treated by surgery alone or surgery with postoperative hyperbaric oxygenation.

We reviewed 41 patients with osteoradionecrosis of the mandible. Each patient was treated by radical resection followed by external beam irradiation. The diagnosis of infected osteoradionecrosis was confirmed clinically, radiologically, and histologically. After operation had failed, 20/41 were given hyperbaric oxygen (HBO) as in 'salvage' treatment. Daily sessions of HBO 2.5 ATA for 60 minutes (mean: 29 sessions) were given. The other 21 patients were treated by operation and antibiotics alone. HBO group (n = 20): The overall success rate for HBO after operation had failed was 13/20. Repeated debridement as first-line treatment followed by postoperative HBO was successful in 12/19. In seven of 19 patients, partial mandibulectomy and microvascular transplantation were required as second-line treatment, and this was successful in five. Primary partial mandibulectomy and microvascular transplantation followed by HBO was successful in 1 patient. Non-HBO group (n = 21): Repeated debridement was successful in 10/11 patients. Partial mandibulectomy was required as second-line treatment in the remaining one. In the other 10, partial mandibulectomy and microvascular transplantation were successful as first-line treatment in four. In the remaining six, further surgical intervention became necessary and were successful for 5-17 months (mean: 13). With a success rate of 13/20, we do not recommend HBO for the treatment of osteoradionecrosis.

Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung--a PCR-based study on four cases.

Sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of Mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial DNA. In three cases sequence analysis was also performed. One patient was negative for mycobacterial DNA in explanted, but positive for M. tuberculosis DNA in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis DNA, but were positive for MOTT-DNA in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial DNA. In cases of recurrent MOTT-DNA-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-DNA-positive sarcoidosis is more likely to recur in a transplanted lung.

Unbalanced chromosomal aberrations in neuroendocrine lung tumors as detected by comparative genomic hybridization.

Typical and atypical carcinoids (TC, ATC) and small (SCLC) and large cell neuroendocrine carcinomas (LCNEC) constitute the spectrum of neuroendocrine lung tumors. Chromosomal aberrations have not been studied in LCNEC and only rarely in carcinoids. Only SCLCs have been investigated frequently for chromosomal aberrations. We compared three typical and four atypical carcinoids, one atypical carcinoid/SCLC mixed type, three SCLC, and three LCNEC for chromosomal gains and losses using comparative genomic hybridization. Typical carcinoids showed either no changes or only few chromosomal gains. Atypical carcinoids appeared genetically heterogeneous: One case had no aberrations, and three cases had few aberrations; two of them showed a deletion of 11q. SCLC and LCNEC were characterized by many gains and losses, especially similar changes of 3p, 5q, 5p, and 13q. Although ATC resemble LCNEC morphologically, there were no similarities at the genetic level. We have found a reciprocal relationship of prognosis and the amount of aberrations. TCs and ATCs with few chromosomal changes have the best prognosis, whereas SCLCs and LCNECs were generally characterized by a great amount of aberrations and worst prognosis. There was no unbalanced aberration common in all types of neuroendocrine tumors of the lung.

Multiplex polymerase chain reaction for rapid detection of atypical mycobacteria and Mycobacterium tuberculosis complex.

A three-step polymerase chain reaction (PCR) method was developed for the detection and typing of mycobacterial DNA in clinical samples and fixed tissue specimens. The first step was to rule out or prove the presence of DNA of Mycobacterium tuberculosis complex. An amplified fragment from the insertion sequence (IS) 6110 was used for this purpose. Patients negative for IS 6110 were evaluated for a fragment of the 65 kDa-antigen, present in all mycobacteria. In positive patients, a multiplex PCR was performed for M. gordonae, M. avium, M. kansasii, M. fortuitum, and M. malmoense, combined in one PCR run. As another control, to prove mycobacterial DNA, PCR was used for the gene coding for the 16S ribosomal RNA also found in all mycobacteria. Appropriate negative controls were included. Different clinical samples were compared for an efficient amplification of these different mycobacterial DNA fragments. Different mycobacteria can be identified within one day in either unfixed cytologic and bacteriologic samples, or formalin-fixed paraffin-embedded tissue samples. Therefore, this method is a quick, cost efficient, and reliable tool to identify mycobacteria other than the tuberculosis complex.

Presence of mycobacterial DNA in sarcoidosis.

In 11 of 35 clinically proven cases of sarcoidosis, we detected DNA sequences coding for the mycobacterial 65-kDa antigen. In four cases, the sequences were homologous to Mycobacterium avium; seven sequences were related to other nontuberculous Mycobacteria. The insertion sequence 1110, characteristic for Mycobacterium avium, was present in three cases. The insertion sequence 6110 of the Mycobacterium tuberculosis complex (M tuberculosis, africanum, bovis, BCG) was not detectable in any of the 11 cases, ruling out the presence of members of the Mycobacterium tuberculosis complex. Therefore, it seems reasonable to speculate about a mycobacterial cause in some cases of sarcoidosis.

Clinical features and therapy of "typical" and "atypical" bronchial carcinoid tumors (grade 1 and grade 2 neuroendocrine carcinoma).

Between 1971 and 1992, 55 patients with grade 1 (G1) (n = 32) or grade 2 (G2) (n = 23) neuroendocrine bronchial carcinomas (males: 26, females: 29; mean age: 47.7 years, range: 13-77 years) were treated. The sexes were evenly distributed in the two groups. Patients with G1 were significantly younger than those with G2 tumors (43.3 vs 53.7 years; P < 0.05). There were no statistically significant differences between G1 and G2 concerning peripheral or central localization, laterality or maximum tumor diameters. Patients with G1 had a higher incidence of tumor-related symptoms and a longer mean duration of these symptoms (21.8 months) than G2 cases (14 months) but the differences were not statistically significant either. No case displayed any symptoms of hormonal activity. Fifty-two patients underwent resection, one was non-resectable for anatomical, and one for functional, reasons; a third refused an operation. We performed 8 pneumonectomies, 36 lobectomies (8 by using bronchoplasty), 2 bronchotomies and 6 segmental resections. Twelve G2 cases had N1 or N2 lymph node metastases, two intrapulmonary metastases were removed. After a median observation time of 55.7 months the 10-year survival rate for the total collective is 90.6%. For G1 it is 100%, compared with 76.4% for G2 patients, 3 of whom died of the tumor (P < 0.05; significant). In univariate analysis: age over 48 years, lymphatic invasion, and lymph node metastasis were also significantly correlated with a poor survival rate. Multivariate analysis proved lymphatic permeation to be the only independent prognostic factor (the survival rate was 100% where there was no invasion, but only 74% where this had occurred).