Is oropharyngeal anaesthesia with topical lignocaine useful in upper gastrointestinal endoscopy?

The aim of this study was to determine whether patients' tolerance of upper gastrointestinal endoscopy is related to the dose of lignocaine spray used for oropharyngeal anaesthesia and to measure plasma concentrations at these doses. Sixty consecutive patients undergoing routine upper gastrointestinal endoscopy with sedation were randomized to receive lignocaine spray 50 mg (Group A), 100 mg (Group B) or 200 mg (Group C). Patient, endoscopist and endoscopy nurse were unaware of the variation in dose used. Each patient's tolerance of the intubation and of the remainder of the gastroscopy was assessed independently by the patient, endoscopy nurse, and endoscopist using a visual analogue scale. Plasma lignocaine concentration was measured at 20, 40, 60 and 80 min after administration of the spray. Fifty (83%) patients were unable to recall either the intubation, or the procedure. On the endoscopy nurse's assessment, the patients in Group B tolerated the intubation better than those in Group A, and Groups B and C tolerated the remainder of the gastroscopy better than those in Group A. On the endoscopist's assessment, Groups B and C tolerated the remainder of the gastroscopy better than Group A. There were fewer gags per min in Groups B and C compared to Group A. Mean plasma lignocaine concentrations showed a dose-dependent absorption of the spray, but none exceeded the potentially toxic level of 5 mg/L.


The effects of flumazenil on alertness and hypoxia in elderly patients after ERCP.

It is not known whether hypoxia, associated with upper gastrointestinal endoscopic procedures when midazolam sedation is used without narcotics, persists into the post-procedure recovery period. Thirty consecutive patients aged over 60 years, undergoing ERCP using midazolam sedation alone, were monitored clinically and by pulse oximetry before, during and for 2 hours after the procedure. They were randomized prospectively to receive either 0.5 mg flumazenil or normal saline on extubation. Results show that patients were most hypoxic in the first 30 minutes after the procedure and that mean oxygen saturation had not returned to pre-sedation values by 2 hours. Treatment with flumazenil increased alertness 2 minutes after the procedure, and was associated with a significantly higher arterial oxygen saturation at 15 minutes.


Short report: omeprazole plus antibiotic combinations for the eradication of metronidazole-resistant Helicobacter pylori.

Twenty-eight Helicobacter pylori-positive patients with metronidazole-resistant isolates and 25 with metronidazole-sensitive isolates were treated for 14 days with 40 mg omeprazole nocte plus 500 mg amoxycillin t.d.s. Eradication of H. pylori, defined as absence of the organism one month after cessation of treatment, was assessed using the [14C]urea breath test. The eradication rate in patients with metronidazole-resistant isolates was 14/28 (50%) while that in patients was metronidazole-sensitive isolates was 12/25 (48%). In contrast to these encouraging eradication rates, very poor results were obtained with a 7-day course of omeprazole (40 mg nocte) in combination with erythromycin ethylsuccinate (500 mg q.d.s.) and tripotassium dicitrato bismuthate tablets (120 mg q.d.s.). The latter eradication rates were 3/20 (15%) in patients taking erythromycin tablets and 3/19 (16%) in those taking a liquid formulation of erythromycin. All treatment regimens were well tolerated and all patients completed the prescribed course of therapy.


[A clinical study of Kaposi's sarcoma associated with the acquired immunodeficiency syndrome].

We have retrospectively studied 35 cases of Kaposi's sarcoma in 460 patients with AIDS (incidence of 7.6%) during a period of 10 years. All of them were males, with a mean age of 38 years. 88% of the cases belonged to the homosexual risk group. The tumor was the diagnostic criteria of AIDS in 25 patients. At the moment of the diagnosis, 4 patients were at stage I, 23 at stage II, 1 at stage III and 7 at stage IV, according to the Mitsuyasu's classification; 7 patients had systemic symptoms. The tumor was localized at the skin (34 cases), mucosa (16), digestive tract (7), lung (6) and ganglion (4). The immunological study revealed lymphopenia in 74% of patients, reduction of T4 lymphocytes ( < 0.5 x 10(9)/L) in 93% and inverted T4/T8 ratio in 96%. Sixteen patients received antitumoral treatment (8 with chemotherapy, 7 with interferon and 5 with radiotherapy). The response was stabilization of lesions in 8 cases, partial remission in 2 and progression in 3; in other 3 cases, such response was not assessed. The mortality was 48% and the average survival, 13 months. Opportunistic infections were the cause of death in most patients. Our results confirm the clinical and evolutive characteristics of the Kaposi's sarcoma associated to AIDS; disseminated cutaneous affectation with frequent visceral affectation, poor response to treatment and low survival associated to the presence of opportunistic infections. The lower incidence of tumor observed in our study is related to the different distribution of the risk groups for HIV in our country.


[Anticardiolipin antibodies in women with habitual abortion. A case-control study].

According to case and control studies we determine the prevalence of anticardiolipin antibodies (ACA) and autoimmune phenomena in 23 women with recurrent abortions (two or more) without apparent cause after study, using as pattern a sample of 86 patients belonging to different subgroups: 21 women with only one abortion, 15 with toxemia, 30 healthy pregnants and 20 healthy non-pregnants. We found that 6 (26%) of the cases with recurrent abortions showed high ACA-IgG versus 6 (7%) of the control group (p = 0.009), with an odds ratio (OR) of 4.7 (Confidence Interval [CI] 95%, 1.4-15). We didn't find a relation with ACA-IgM, OR or 2.2 (CI 95%, 0.72-6.50; p = 0.160). Our patients only showed as manifestation of antiphospholipid antibodies syndrome, recurrent abortions, finding neither association with thrombotic phenomena, nor thrombocytopenia. They didn't show either clinical or analytical manifestations of autoimmune disease. We concluded that the ACA-IgG can be associated to the fetal loss in these kind of patients.


[The results of a program of preoperative hospital assessment of geriatric patients].

In order to illustrate the possibilities that offers the specialized geriatric evaluation during the preoperative period of elderly patients in a general hospital, the results obtained throughout two years are presented and compared, according to preestablished design, in 551 urological patients (U) (age: 75.4 years) and 597 traumatological patients (T) (age: 79 years), all of them over 65 years old. The more frequent interventions were hip fractures (88% of T), prostatic adenoma and vesical urothelioma (42 and 27% of U). Only in 10% of T and 18% of U, we did not observed related problems. The most frequent of these were cardiovascular, neuropsychiatric and respiratory problems, especially in group T. Some kind of recommendations were given in 88% of T and 80% of U. The average period in taking care of these inter-consultations was 1.3 days and the number of perioperative visits was 2.4. In 42% of T and 74% of U, we did not observe psychical discapacities. The average surgical risk measured by the ASA was grade III or IV in 22% of T and 12% of U, similar figures than the ones of the cardiac risk (Goldman). We believe that this type of specialized evaluation is more comprehensive and renders important benefits both for the elderly patients and for the surgeon, when compared with the traditional system of preoperative evaluation.


[Changes in the mechanism of action of insulin on fatty tissue accumulations in lipomas, Madelung's lipomatosis and liposarcoma].

In this paper, the preliminary results regarding the alterations of the biological action mechanism of insulin in several types of pathological accumulations of fat, i.e. lipomas, Madelung's Lipomatosis and liposarcoma, are presented. The results indicate significant alterations both at the insulin receptor and post-receptor levels, with reduced biological activity of this hormone, which could have and inductive role in the pathogenesis of such entities.


[Malignant angioendotheliomatosis associated with an acute confusional syndrome: a case report and review of the literature].

We present a case of malignant angioendotheliomatosis (MAE) localized at the central nervous system (CNS) in a 74-years-old male, manifested as an acute confusional syndrome with fever, characteristics of lymphocytic meningitis in the cephalorhachidian liquid (CRL) and dilatation of the left lateral ventricle according to the cranial computerized tomography (CT). The diagnosis was established using post-mortem immunohistological techniques, concluding that it was an intravascular lymphomatous process with secretion of immunoglobulins.


[Bronchiolitis obliterans with organized pneumonia: apropos 2 new cases].

We present two cases of bronchiolitis obliterans organizing pneumonia (BOOP) with different clinical and radiological characteristics. In one case, the chest X-ray demonstrated bilateral migrating infiltrates. The pathology showed bronchiolar and intra-alveolar occupation by granulation tissue in both cases. It should be noted that both patients responded well to treatment with prednisone although alterations in gas exchange persisted in one case.


[Q fever and endocarditis. Apropos a new case].

Endocarditis is the first manifestation of Q fever in its chronic form, generally affecting prosthetic cardiac valves or previously injured valves. Its clinical presentation is an endocarditis with negative culture and there is not agreement with regard to the most adequate antimicrobial treatment and its duration. Frequently, the valve has to be replaced. We present a case of a patient with double aortic lesion, in whom endocarditis by Q fever was diagnosed and treated with doxycycline, initially with success. However, she relapsed one year later, being then resistant to the medical treatment (doxycycline, ciprofloxacine plus rifampicine). It was not possible to replace the valve and the patient died two months later due to cardiac failure.


[Bronchoalveolar lavage in respiratory pathology].

Bronchoalveolar lavage (BAL) offers great opportunities in the study of pulmonary diseases. It is safe and noninvasive technique, with similar possibilities than other invasive diagnostic methods and allo-wind repetitions. With the obtained sample, we can assess what happens at the bronchial level as well as the alveolar structures. The introduction of new study methods has increased its profitability in several respiratory pathologies: analysis of tumoral markers in lung cancer, monoclonal antibodies in histiocytosis X, and so on. The BAL can be considered a technique of diagnosis, follow-up, prognosis and evaluation in pulmonary diseases.


Management of women with a cervical smear showing a mild degree of dyskaryosis: a review of policy.

Three hundred and thirty-seven women who presented for the first time with a cervical smear showing a mild degree of dyskaryosis were followed for a minimum period of 3 years and 9 months. Of the 305 women with complete cytological and histological records, 178 were biopsied and 127 remained on cytological follow up. In the biopsied group one case of microinvasive squamous cell carcinoma was diagnosed within 1 year of the patient's first abnormal smear. A further 24% showed cervical intraepithelial neoplasia (CIN) I, 17% showed CIN II and 29% showed CIN III. The overall regression rate for the group of 305 women was 34%. Our results indicate that cytological surveillance is acceptable provided that biopsy is advised when dyskaryosis persists. No major modifications to laboratory policy are indicated and in approximately 34% of cases an unnecessary hospital referral would be avoided.


Immunocytochemical detection of the androgen receptor in fine needle aspirates from benign and malignant human prostate.

A monoclonal antibody to the androgen receptor was applied to fine needle aspirates from patients with benign and malignant prostatic disease. The series includes six patients with benign hyperplasia and 24 patients with prostatic carcinomas. The androgen receptor was detected in most nuclei of both benign and malignant epithelial cells. The intensity of immunostaining varied. No obvious relation was observed between the intensity of the staining in benign versus malignant cells. In addition no clear differences were found in the proportion of androgen receptor positive cells in benign aspirates as compared with aspirates from well differentiated or moderately well differentiated prostatic carcinomas. The relative number of androgen receptor positive cells was highest in smears from poorly differentiated prostatic carcinomas.


Necrotic debris in thyroid aspirates: a feature of follicular carcinoma of the thyroid.

Fine needle aspirates from 44 follicular thyroid tumours (30 adenomas, 14 carcinomas) have been studied. All aspirates contained neoplastic cells in follicular and trabecular arrangements. The individual tumour cells showed varying degrees of anisonucleosis and nuclear pleomorphism. Colloid was scanty or absent from all smears. Granular or filamentous necrotic material was observed in both biopsies and smears from one moderately and two poorly differentiated follicular carcinomas, but in none of the adenomas. This suggests that necrotic debris may be a feature of follicular carcinoma of the thyroid.


Fine needle aspiration cytology of high grade T-cell lymphomas in human T-lymphotropic virus type 1 carriers.

We studied the fine needle aspiration (FNA) cytology of high grade peripheral T-cell lymphomas from eight human T-lymphotropic virus-1 (HTLV-1) positive patients. FNA smears from seven lymphomas showed a distinctive cytologic pattern with a dominance of rounded cells with irregular nuclei and a moderately basophilic cytoplasm. Irregular cells with a pale abundant cytoplasm were present in varying amounts. Some smears contained a few giant cells with cerebriform nuclei. In addition, plasma cells and eosinophils were found. Epithelioid cells were an inconstant finding. On histology these seven lymphomas were assigned to the pleomorphic medium-large cell subtype and all but one were of T-helper phenotype with rearrangements of the T-cell receptor. FNA smears from a lymph node in a patient with a previous histological diagnosis of lymphomatoid papulosis of the gingiva showed a monotonous pattern of large immunoblastic cells with some binucleated variants consistent with a diagnosis of high grade immunoblastic lymphoma, which was confirmed histologically. Our results show that peripheral T-cell lymphomas from HTLV-1 positive patients have cytological patterns which are distinctive enough to allow a conclusive diagnosis of high grade T-cell lymphoma. However, we do not think that the cytology of HTLV-1 positive lymphomas can be differentiated from that of virus-unrelated high grade T-cell lymphomas.


Acinic cell tumour: a metastasis in the lung diagnosed by electron microscopy of aspirated material.

A case of acinic cell carcinoma, metastatic to lung is presented. Fine needle aspiration showed a low-grade adenocarcinoma. Electron microscopy of the aspirated material, however, allowed definite preoperative diagnosis of metastatic acinic cell carcinoma. The lesion was successfully resected and diagnosis confirmed on histology. Ten years previously an acinic cell carcinoma of similar histology had been excised from the left parotid region.


Spontaneous infarction of an intraductal papilloma of the breast: cytological presentation on fine needle aspiration.

A relatively rare case of spontaneous infarction of an intraductal papilloma of the breast is presented which was considered to be suspicious for malignancy on fine needle aspiration (FNA) cytology. The aspirate revealed several groups of atypical cells featuring a high nuclear-cytoplasmic ratio, coarsely granular chromatin, and somewhat prominent nucleoli. There was abundant necrotic cellular debris in the background. These cellular features were considered evidence of ductal carcinoma of the breast. The correct diagnosis was made by open biopsy which revealed necrosis involving the breast due to infarction of an intraductal papilloma.


Fine needle aspiration cytodiagnosis of a carcinoid tumour of the male breast.

The diagnosis of a primary carcinoid tumour of the breast in a 38-year-old male was initially made from a fine needle aspiration sample. The cytodiagnosis was supported by the histochemical demonstration of Grimelius-positive granules in tumour cells which were also found in tissue removed in a subsequent biopsy. An immunocytochemical study using markers for neuron-specific enolase and chromagranin in the aspirated sample and tissue was found to be negative. A total mastectomy with axillary node dissection was performed which showed no residual or metastatic tumour. No primary tumour was found elsewhere.


Stimulation of pyloric contractions by intraduodenal triglyceride is persistent and sensitive to atropine.

Intraduodenal lipid infusion stimulates phasic and tonic pyloric contractions and suppresses antral contractions. This study determined: (i) whether this response is sustained over 90 min; and (ii) the role of muscarinic mediation of this response. Antropyloroduodenal motility was recorded in 17 healthy volunteers with a sleeve/sidehole manometric assembly. Subjects received either a 90 min intraduodenal infusion of saline or triglyceride (20% Intralipid) at a rate of 1 mL/min; 30 min after the start of this infusion, the eight subjects who received triglyceride were given intravenous atropine 15 micrograms/kg over 30 s, followed by a maintenance infusion of 4 micrograms/kg/h until the study was completed. Intraduodenal triglyceride infusion stimulated isolated pyloric pressure waves consistently, producing a median rate of 2.4 per min after 30 min of triglyceride infusion, compared with a median rate of 0 per min pre-infusion. In intravenous saline studies, there was a reduction (P < 0.05) in the median rate of isolated pyloric pressure waves to 1.3 per min at 90 min, when compared with pyloric pressure waves at 30 min. Atropine reduced isolated pyloric pressure waves to a median rate of 0 per min, significantly different from preatropine (P < 0.01) and from intravenous saline studies (P < 0.0001). These results indicate that the phasic pyloric response to intraduodenal lipid persists during 90 min stimulation, albeit with significant attenuation. In humans, muscarinic cholinergic blockade prevents the occurrence of triglyceride stimulated localized pyloric contractions.


Field evaluation of a rapid, simple and inexpensive urease test for the detection of Helicobacter pylori.

A modified rapid urease test (MRU test) for the detection of Helicobacter pylori was evaluated under field conditions during an endoscopic survey in rural India and compared with a commercially available urease test (CLO test) and with histology. Of 195 consecutive subjects who underwent upper gastrointestinal endoscopy, 153 (78.5%) were positive for Helicobacter pylori when tested by the CLO test and/or histology. The sensitivity and specificity of the MRU test relative to this was 97.4 and 95.2%, respectively when the test was read over a 3 h period. The MRU test was positive in 77.4, 89.0, 93.8 and 96.6% of cases at 1, 5, 20 and 60 min, respectively, compared with 2.7, 14.4, 48.6 and 71.2% of cases for the CLO test at the same time. The accuracy of the MRU test was thus similar to that of other methods for the detection of Helicobacter pylori. Furthermore, it gave a positive diagnosis more rapidly than other tests, in most cases before the subject had left the endoscopy suite. The MRU test is extremely simple to prepare and read and costs less than 0.05 pounds per test compared with 2.26 pounds for a CLO test. It is suitable for use in clinical or epidemiological work and especially where cost factors are critical.


Adaptation of rat gastric mucosa to repeated doses of non-salicylate non-steroidal anti-inflammatory drugs.

To determine whether gastric mucosal adaptation occurs to the damaging effects of repeated non-steroidal anti-inflammatory drug (NSAID) administration, we compared the extent of gastric damage in rats after single or repeated doses of four non-salicylate NSAID. With daily dosing, adaptation occurred only to repeated doses of the short-acting NSAID ibuprofen and diclofenac but not to indomethacin and naproxen, both of which have considerably longer half-lives. Adaptation to indomethacin was demonstrable if the dosage interval was lengthened and the drug was given on alternate days rather than daily. Histological examination of the gastric mucosa of diclofenac-treated rats showed a similar degree of superficial damage in the single and repeatedly dosed groups. However there was a highly significant reduction in the amount of deeper mucosal damage in the repeatedly dosed rats. Our findings show that under certain conditions of dosage, adaptation to non-salicylate NSAID is demonstrable. The pharmacokinetics of individual NSAID appear to be important in determining whether or not adaptation occurs. Histological examination showed that adaptation to one of the shorter acting NSAID, diclofenac, was characterized by a significant reduction in deeper mucosal damage.


Factors influencing the fate of T cells responding to Mls antigens.

Although T cell tolerance to self antigens is primarily a reflection of clonal deletion in the thymus, recent evidence suggests that mature T cells are subject to negative regulation in the post-thymic environment: Extrathymic tolerance is the result of clonal anergy in some studies and T cell deletion in others. The factors controlling the induction of anergy versus deletion of mature T cells are still poorly understood. This article summarizes evidence that exposure of T cells to Mls superantigens in vivo leads to a sequence of T cell proliferation, anergy and deletion; anergy appears to reflect persistence of antigen. The biochemical consequences of exposing T cells to superantigens in vitro are discussed.


Clinical significance of the serum levels of the 7S domain of type IV collagen in patients with primary biliary cirrhosis.

The serum levels of the 7S domain of type IV collagen were measured with a radio-immunoassay in 42 patients with primary biliary cirrhosis (asymptomatic: n = 28; symptomatic: n = 14), 10 patients with chronic active hepatitis, 10 patients with liver cirrhosis and 10 healthy female controls. Serum levels of the 7S domain of type IV collagen were: 4.28 ng/mL (3.88-4.72 ng/mL; mean and range of mean +/- s.d.) in healthy controls; 5.97 ng/mL (5.07-7.02 ng/mL) in patients with chronic active hepatitis; 8.23 ng/mL (6.40-10.58 ng/mL) in patients with liver cirrhosis; and 6.79 ng/mL (4.76-9.67 ng/mL) in patients with primary biliary cirrhosis. Patients with liver cirrhosis and primary biliary cirrhosis had higher levels of serum 7S domain of type IV collagen than healthy controls (P < 0.001, respectively). Serum levels of the 7S domain of type IV collagen in patients with asymptomatic primary biliary cirrhosis, 5.83 ng/mL (4.55-7.48 ng/mL) were significantly lower than those in symptomatic primary biliary cirrhosis, 9.18 ng/mL (6.53-12.91 ng/mL; P < 0.001). Serum levels of the 7S domain of type IV collagen increased significantly along with advancement of the histological stages of primary biliary cirrhosis. Serum levels of the 7S domain of type IV collagen in the paired sera of eight patients with asymptomatic primary biliary cirrhosis (mean interval 30 months, range 12-48 months) showed significant rises during the intervals (P < 0.05), while serum levels of albumin and total bilirubin did not change significantly during these intervals.(ABSTRACT TRUNCATED AT 250 WORDS)


Double-blind comparison of omeprazole 20 mg OM and ranitidine 300 mg NOCTE in duodenal ulcer: a Taiwan multi-centre study.

Two hundred and twenty-six patients with endoscopically confirmed duodenal ulcers > or = 5 mm in diameter entered a double-blind randomized trial comparing 20 mg omeprazole administered once daily in the morning with 300 mg ranitidine administered once daily at night. The patients were assessed endoscopically and symptomatically after 2 weeks, and those whose ulcers had healed terminated the study. Patients with unhealed ulcers continued treatment for a total of 4 weeks. Omeprazole produced significantly higher healing rates than ranitidine at both 2 weeks (57 vs 28%, P < 0.0001) and 4 weeks (93 vs 80%, P = 0.006). Similarly, significantly higher 'effective healing rates' (defined on the criteria established by the Japanese Society of Digestive Endoscopy) were observed with omeprazole compared with ranitidine at 2 and 4 weeks. After 2 weeks, there were significantly fewer reports of both day-time and night-time epigastric pain by omeprazole-treated patients compared with ranitidine-treated patients (22 vs 44%, P < 0.0001 for day-time pain; 24 vs 35%, P = 0.025 for night-time pain). Both drugs were well-tolerated and no major adverse effects were recorded during either treatment. In conclusion, 20 mg omeprazole administered once daily was superior to 300 mg ranitidine administered once daily for duodenal ulcer healing and symptom relief.


Gall-bladder sludge: lessons from ceftriaxone.

Ceftriaxone-associated sludge has been a fascinating story. The occurrence is novel and unique. It has produced a model of gall-bladder sludge in humans. This phenomenon has taught us a great deal about biliary lipid and organic anion excretion by the liver, and the physical chemistry of calcium and calcium sensitive anions. It has added further insights into the pathophysiology of gall-bladder sludge formation. It points to a combination of a hepatic effect where the liver secretes a biochemically abnormal bile, and a gall-bladder effect which provides an environment for precipitation, in order for sludge to develop. The precipitated calcium ceftriaxone has prompted us to re-evaluate the imaging criteria for the diagnosis of gall-bladder sludge versus gallstones. Above all, the rapid onset and rapid disappearance of ceftriaxone sludge has mirrored in a compressed, encapsulated form, the natural history of gall-bladder sludge. It has reminded us that, like gallstones, biliary sludge is usually benign and asymptomatic. However just because it is smaller than gallstones does not mean it cannot cause problems. It can disappear or it can become a calcium ceftriaxone gallstone.


Protective effects of a prostaglandin E1 oligomer on taurocholate-induced rat pancreatitis.

Effects of prostaglandin E (PGE) on acute pancreatitis have been controversial. This study shows the effects of PGE1 oligomer, MR-356, on trypsin-taurocholate-induced acute pancreatitis in rats. Divided intraperitoneal doses of 0.6 mg/rat were administered, which increased 24 h survival rates when the oligomer was given both at 1 h before and after (group A) and immediately and 3 h after (group B) induction of pancreatitis. In group A MR-356 significantly improved the survival rates at 18 h (94 vs 61%, P < 0.05) and 24 h (68 vs 33%, P < 0.05) when compared with controls. MR-356 improved the survival rates dose-dependently up to 0.6 mg/rat when given by the same protocol of group A. In group B MR-356 also improved the survival rate (72 vs 39%, P < 0.05) only at 24 h, while other parameters failed to improve. The present results suggest that the PGE1 oligomer may play a beneficial role in bile-induced pancreatitis, probably through its proposed effects of stabilization of lysosomal membranes, maintenance of microcirculation and inhibition of protease in the pancreas.


A review of postgastrectomy bone disease.

Postgastrectomy bone disease was a term devised to describe the metabolic disorders of bone which may follow a gastrectomy operation. Although the use of this operation has declined drastically in recent years, this metabolic bone disorder is still with us and may escape and confuse the unwary. These disorders may take the form of osteomalacia, osteoporosis in excess of normal ageing, or a combination of both. For screening purposes, regular estimations of plasma alkaline phosphatase levels identify patients who may be developing osteomalacia which can then be treated with calcium and vitamin D supplements. Numerically, osteoporosis in excess of ageing is a bigger problem and its prevention and treatment is at present unsatisfactory. Screening procedures for osteoporosis are reviewed, including the more recent methods of bone mineral density assessment. Osteopenia or demineralization occurs in both osteomalacia and osteoporosis therefore osteomalacia must be excluded before attributing any loss to osteoporosis. The present situation with regards to the prevention and treatment of osteoporosis is also reviewed.


Effects of long-term bilateral and unilateral fitting of different hearing aid types on the ability to locate sounds.

Aided localization ability of 87 hearing-impaired listeners was tested for horizontal and vertical sound sources, at two signal levels, and for two orientations to the loudspeaker array (facing, sideways). Some listeners wore behind-the-ear (BTE) aids, others in-the-ear (ITE) aids. Some were bilaterally fitted, others unilaterally fitted. Listeners were tested only with types of aids and fittings that they were accustomed to wearing. The results strongly supported bilateral fitting for moderately and severely hearing-impaired listeners. However, for mildly impaired listeners, those fitted unilaterally performed as well, on average, as those fitted bilaterally. This suggests a need to consider individual listening requirements and also to provide such listeners with experience in unilaterally-aided listening before assessing the possible advantages of bilateral fitting. When hearing level was controlled, there was no overall difference in the performance of ITE and BTE aid wearers. This discrepancy with other research may be explained by measures (removal of intensity cues, permitting of head movement) designed to make the test situation more representative of real-life listening.


New trends in non-absorbable antibiotics in gastrointestinal disease.

Numerous antibiotics have been used for several years in the treatment of intestinal diseases, the majority belonging to the class of aminoglycosides. These are effective against gram-positive and some gram-negative bacteria, above all aerobes, and do not therefore cover the entire range of microorganisms responsible for intestinal infections. With these antibiotics, moreover, it is not possible to exclude intestinal absorption which can lead to serious side effects. Other intestinal antibiotics, however, such as Vancomycin, have a restricted spectrum of action which limits their use. This study analyzes the pharmacological characteristics of a new non-absorbable antibiotics with particularly interesting properties from a clinical pharmacokinetic and pharmacodynamic point of view: Rifaximin. This drug has an extremely broad spectrum of action covering all intestinal germs, and its absorption is practically zero. The results of some controlled clinical studies in gastrointestinal diseases are examined, such as the treatment of infectious diarrhoea, of acute or chronic portal-caval encephalopathy and of diverticular disease of the colon. The possible role of Rifaximin in some intestinal diseases, such as small bowel bacterial overgrowth and Crohn's disease and ulcerative colitis, is also analyzed.


Maximum length sequence auditory evoked brainstem responses in human newborns and adults.

Experiment 1 investigated developmental differences at high stimulus rates by using maximum length sequences (MLSs) and cross-correlation techniques to recover auditory evoked brainstem responses (ABRs). Reliable MLS ABRs were recorded in all of the newborns tested at the highest rate presented (minimum interpulse interval = 1.1 msec). Interpreting developmental rate effects from latency and amplitude shifts is problematic. Identification of higher order kernals offers new information concerning developmental rate effects. Kernel slices were measured at lower rates in more adults than newborns, suggesting that the newborn auditory system is less sensitive to temporal nonlinearities than the mature auditory system. This runs counter to developmental rate studies using conventional stimuli. Experiment 2 investigated developmental differences at high rates due to varying stimulus intensities. MLS wave V intensity functions were less steep than conventional wave V intensity functions. MLS thresholds were also higher than conventional thresholds (primarily due to the newborn data). Without equating for signal-to-noise ratio, it is difficult to make unambiguous conclusions concerning the observed developmental differences.


Adult-onset auditory deprivation.

Adult-onset auditory deprivation following prolonged lack of amplification in the unaided ears of persons with bilaterally symmetrical sensorineural hearing impairment was first reported in 1984. This article on the phenomenon includes a review of the literature on adult-onset auditory deprivation in relation to etiology, pathophysiology, hearing-loss manifestations, typical audiologic profile, amplification strategies, contraindications or challenges to conventional hearing-aid fitting, and future research. A case study illustrates the phenomenon of auditory deprivation from monaural amplification with recovery following binaural amplification. The results of a complete audiologic and acoustic-immittance evaluation are presented for a bilaterally sensorineural hearing-impaired male with adult-onset auditory deprivation who initially was fit monaurally and later was fit binaurally. A significant decrement in the suprathreshold word-recognition scores occurred only in the unaided ear following monaural amplification, illustrating the phenomenon of adult-onset auditory deprivation. Following binaural amplification, the suprathreshold word-recognition scores for the formerly unaided ear improved significantly, illustrating the phenomenon of recovery from the adult-onset auditory deprivation with binaural amplification.


Requirements for the use of intestinal action antibiotics in the treatment of ulcerative colitis.

The causes of ulcerative colitis are still unknown and above all the circumstances which can lead to inflammatory episodes are unclear. Antibiotic therapy has not provided encouraging results so far but it is possible that the pathogenesis of this disease may involve bacterial species which have not yet been identified. The use of an antibiotic with specific colic activity therefore seems to be justified.


Early detection of ototoxicity using high-frequency, tone-burst-evoked auditory brainstem responses.

Subjects receiving treatment with ototoxic agents were evaluated concurrently with conventional and high-frequency (> or = 8 kHz) behavioral threshold measures and with ABR to click and to 8, 10, 12, and 14 kHz tone-burst stimuli. Behavioral threshold data revealed ototoxic change in 51 percent of ears evaluated. Of these ears demonstrating behavioral change, 90 percent revealed concurrent ABR changes. If only ABR monitoring with high-frequency tone-burst stimuli had been used, 87 percent of allears showing behavioral change would have been identified. Three fourths of these would have been identified from wave V responses, with 87 percent identified from the two highest frequencies tested for each individual. This research suggests that behavioral change is reflected accurately in the ABR, that high-frequency tone bursts will identify a majority of initial ototoxic changes, and that monitoring hearing with high-frequency, tone-burst-evoked ABRs during treatment with potentially ototoxic agents is significantly more effective than click-evoked ABRs for early detection of ototoxicity.


Non-absorbable antibiotics and small bowel bacterial overgrowth.

The normal gastrointestinal flora includes no more than 10(3) organisms/ml of gastric aspirate and no more than 10(5) organisms/ml of duodenal or jejunal juice. The organisms are primarily gram-positive and aerobic bacteria. In particular anatomical or functional predisposing conditions, an abnormal colonization takes place in the small bowel with microbial concentrations > or = 10(7)/ml of aspirate and with a predominance of anaerobes and coliforms. At times this small bowel bacterial overgrowth remains asymptomatic, but more often leads to a true malabsorption syndrome with symptoms, such as diarrhoea, weight loss and megaloblastic anemia. The most accurate procedure for confirming the presence of this condition is represented by the bacterological analysis of the jejunal aspirate. The routine use of this method is, however, notably hindered by the need for intubation of the patient and by the lack of laboratories suitably equipped for anaerobe culture. As an alternative to this complex procedure, numerous non-invasive tests have been perfected over the last few years, including the glucose- or lactulose- H2 breath test. The main aim of the treatment of the small bowel bacterial overgrowth is the suppression of the bacterial colonization using antimicrobial therapy. Among the local-action non-absorbable antibiotics, rifaximin, was shown to have bactericidal activity against aerobes and anaerobes bacteria, such as bacteroides, lactobacilli and clostrides. In controlled clinical trials the antibiotic has demonstrated therapeutic efficacy in bacterial origin diarrhoea, in porto-systemic encephalopathy, in diverticulosis and, finally, in small bowel bacterial overgrowth.


Precedence effect and speech understanding in elderly listeners.

It has been reported that many elderly persons exhibit problems in identifying the location of fused auditory images in a test of the precedence effect in sound localization. The precedence effect involves the neural integration of multiple competing binaural temporal cues, and may reflect subtle age-related neural timing or integration problems. This study investigated whether elderly persons who have difficulty with this test also exhibit problems with speech understanding. The speech measures involved a comparison of performance-intensity functions for phonetically balanced (PB) words and for synthetic sentences presented with ipsilateral speech competition (SSI-ICM). The performance of the elderly subjects on the precedence effect test was significantly correlated with the SSI-max scores but not with PB-max. These findings suggest that age-related difficulties in speech understanding may reflect, at least in part, breakdowns in auditory temporal acuity or resolution.


High-frequency thresholds: circumaural earphone versus insert earphone.

Benefits of high-frequency audiometry in monitoring hearing sensitivity of patients administered ototoxic medications are well established. High-frequency thresholds have been reported to be variable, due in part to small differences in the placement of the earphone diaphragm over the opening of the ear canal. Reliability may be improved by using insert earphones (ER-2) when obtaining high-frequency thresholds. The purposes of this study were to determine high-frequency threshold test-retest reliability using Koss HV/1A+ and ER-2 earphones and to determine if significant differences are present between high-frequency thresholds obtained using these two earphones. Results obtained on 40 ears of 20 normal hearing adults revealed that differences between the test and retest thresholds for each earphone were not significant. Intrasubject threshold differences between the test and retest thresholds for each earphone were, for the most part, within +/- 10 dB at all test frequencies. Further, significantly greater intensity was required to measure threshold when using the ER-2 earphone when compared to the Koss HV/1A+ at all test frequencies.


Treatment of hepatic encephalopathy with non-absorbable antibiotics.

Hepatic encephalopathy represents a well known neuropsychiatric syndrome in patients with either acute or chronic impaired liver function and is characterized by disturbance of consciousness, personality and intellectual capacity, altered neuromuscular activity and electroencephalographic abnormalities. The pathogenesis of the syndrome is still unknown, although important roles are ascribed to circulating gut-derived toxins of nitrogenous origin and to changing in central neurotransmission. Therefore, treatment is aimed to reduce the production and absorption of gut-derived toxins and to modify central neurotransmission balance. Among the different therapeutic approaches proposed for the management of hepatic encephalopathy, antimicrobial agents, alone or in combination with non-absorbable disaccharides, represent an important step, being able to reduce the production and absorption of ammonia, a compound of key importance in the pathogenesis of hepatic encephalopathy.


Factors affecting speech in patients with isolated cleft palate. A methodic, clinical and instrumental study.

The present study deals with various factors affecting speech, particularly its resonance, in patients with isolated cleft palate. For that purpose a method to evaluate hypernasality was developed. The degree of hypernasality was assessed in terms of hypernasality indexes by means of a modified cul-de-sac hypernasality test. The phonetic content of the test words was chosen so as not to bias the evaluations by compensatory articulations. The reliability and validity of four variations of hypernasality indexes were examined. All these four indexes proved reliable, valid and feasible for evaluating hypernasality. The hypernasality indexes were compared with nasalance scores derived from the Model 6200 Nasometer (The Nasometer 1987, Fletcher et al. 1989). Reference nasalance scores for normal Finnish speech were measured. The mean percent nasalance and the standard deviation were 13 and 8, respectively. In addition to the present hypernasality test modification, more traditional descriptive speech analysis was used in some studies. The effect of the age at primary palatal repair on speech was examined in three year old children with isolated cleft palate. The effect on speech of two techniques for primary palatal repair - a Veau-Wardill-Kilner V to Y push back procedure and the Cronin modification - were compared in young adults with isolated cleft palate. The effect on speech of two techniques for a secondary velopharyngeal flap - a Sanvenero-Rosselli and modified Honig flap - were compared in patients with various ages and cleft types. One third had cleft lip and palate or submucous cleft palate. The rest had isolated cleft palate. The quality of speech was significantly dependent on the age at primary palatal repair. The children, whose palatal repair was performed at the average age of 22 months demonstrated, significantly more frequently, hypernasality and misarticulations related to velopharyngeal insufficiency than the children operated upon earlier. The children operated upon between the average ages of 12-18 months, demonstrated normal speech in about 3/4 of the cases. If the palate was operated on later, about 1/4 of the patients demonstrated normal speech. The technique for primary palatal repair had a significant influence on the quality of speech. Hypernasality assessed in terms of hypernasality indexes was less frequent in the speech of patients with the Cronin modification than with the Veau-Wardill-Kilner push back procedure. The technique for the secondary velopharyngeal flap also affected speech significantly. The patients with a modified Honig velopharyngeal flap eliminated more efficiently hypernasality from their speech than those with a Sanvenero-Rosselli flap.(ABSTRACT TRUNCATED AT 400 WORDS)


Antibacterial drugs in Crohn's disease.

The evidence of a beneficial role of antibacterial drugs in Crohn's disease is largely empirical. Data accumulate to show that these drugs may well be used as an adjunctive therapy to oral anti-inflammatory drugs. Circumstantial evidence has also been provided that antibacterial drugs are effective in relieving symptoms related to bacterial overgrowth and when used for specific indications such as perianal lesions.


Symptoms of gallstone disease.

The most certain symptomatic manifestation of gallstones is episodic upper abdominal pain. Characteristically, this pain is severe and located in the epigastrium and/or the right upper quadrant. The onset is relatively abrupt and often awakens the patient from sleep. The pain is steady in intensity, may radiate to the upper back, be associated with nausea and lasts for hours to up to a day. Dyspeptic symptoms of indigestion, belching, bloating, abdominal discomfort, heartburn and specific food intolerance are common in persons with gallstones, but are probably unrelated to the stones themselves and frequently persist after surgery. Many, if not most, persons with gallstones have no history of pain attacks. Persons discovered to have gallstones in the absence of typical symptoms appear to have an annual incidence of biliary pain of 2-5% during the initial years of follow-up, with perhaps a declining rate thereafter. Gallstone-related complications occur at a rate of less than 1% annually. Those whose stones are symptomatic at discovery have a more severe course, with approximately 6-10% suffering recurrent symptoms each year and 2% biliary complications. The far higher rates of symptom development reported in a few studies raise the possibility that these incidence estimates may be too low. The best predictors of future biliary pain are a history of pain at the time of diagnosis, female gender and possibly obesity. The risk of acute cholecystitis appears to be greater in those with large solitary stones, that of biliary pancreatitis in those with multiple small stones, and that of gallbladder cancer in those with large stones of any number. Drugs that inhibit the synthesis of prostaglandins may now be the treatment of choice in patients with gallstones who are suffering acute pain attacks. Persistent dyspeptic symptoms occur frequently following cholecystectomy. A prolonged history of such symptoms prior to surgery and evidence of significant psychological distress appear to be the best predictors of unsatisfactory outcome.


Bile acid dissolution therapy of gallbladder stones.

Oral cholelitholytic bile acid therapy has become established treatment for selected patients with cholesterol gallstones. The treatment finds its clinical application both alone and in combination with ESWL. UDCA alone or, less commonly, a combination of this bile acid with CDCA is used. Optimal results can be expected only in carefully selected patients. Bile acid dissolution therapy is most successful in patients with radiolucent gallstones which are < or = 0.5 cm in diameter or are shown by OCG to be floating. Dissolution is seldom seen when the stones are > 1 cm in size. Cholelitholytic treatment in combination with ESWL yields optimal results in single radiolucent gallstones which are not greater than 2 cm. ESWL thus makes it possible to use medical treatment effectively in single 1-2 cm gallstones when bile acids alone would not be successful. Bile acid treatment is extremely safe, especially if UDCA is given without the addition of CDCA.


Gallbladder stones: shockwave therapy.

Within the past 7 years, gallbladder lithotripsy by shockwaves has been proven to be a safe and effective non-invasive therapy for selected patients with gallstone disease. While regulatory decisions prevent shockwave therapy from being used more frequently in the USA, the number of patients treated in Europe and Asia is increasing constantly. At our institution, a relatively constant number of about 250 new patients per year have been treated since 1988 (Figure 4). About 20% of patients with gallstones are suitable for shockwave therapy according to present criteria. The rate of evacuation of all fragments is determined by the initial stone number and stone size, the success at stone fragmentation, adjuvant bile acid dissolution therapy, and gallbladder contractility. In contrast to laparoscopic cholecystectomy (Dubois et al, 1989; Perissat et al, 1989; Southern Surgeons Club, 1991), shockwave therapy does not require general anaesthesia. And in contrast to direct contact dissolution therapy of gallbladder stones using MTBE (Thistle et al, 1989), lithotripsy is non-invasive. In the majority of patients, complete fragment disappearance takes several months. Preliminary analyses of the cost-effectiveness of lithotripsy have revealed that lithotripsy, including retreatments and bile acid medication for recurrent stones, costs about as much as open cholecystectomy (Rothschild et al, 1990; Bass et al, 1991). The ideal patient for gallbladder lithotripsy has a single radiolucent stone < or = 20-25 mm in diameter in a functioning gallbladder (Figure 1). In patients with such stones, nearly all studies have confirmed a favourable outcome with rapid clearance of all fragments and a relatively low rate of stone recurrence. For carefully selected patients, extracorporeal shockwave lithotripsy is therefore an attractive non-invasive therapy.


Direct contact dissolution therapy.

Direct contact dissolution using MTBE is a safe, effective treatment for many patients with cholesterol gallstones when performed by clinicians experienced with this technique. This may be the treatment of choice for many patients at high risk for general anaesthesia or surgery. Cholecystostomy using local anaesthesia with subsequent stone extraction is an alternative requiring prolonged catheter drainage, and is associated with some risk and discomfort (Hawkyard et al, 1990). Most experts concur that laparoscopic cholecystectomy cannot be performed safely and comfortably without general anaesthesia under most circumstances. A second small population of patients are inordinately apprehensive about general anaesthesia or surgical removal of their gallbladder and refuse standard therapy in spite of recurrent biliary symptoms. Although direct contact dissolution is generally well tolerated, it may require several days of paramedical attention with medical supervision. This procedure will be most efficiently, effectively and comfortably performed by an experienced team and is, therefore, probably best provided by referral centres with physicians sufficiently interested in the treatment of biliary tract stone disease to develop expertise with this method.


Laparoscopic cholecystectomy: an analysis of 777 cases.

Born in secret in 1987 and developed in an atmosphere of scepticism throughout 1988, laparoscopic cholecystectomy triumphed in 1989 and 1990, causing a veritable revolution in the world of general surgery. The 777 consecutive cases that are reported in this chapter reflect the spirit of these various periods. From conservatively restrictive, our indications widened to include 90% of gallstone cases. For us the sclero-atrophic gallbladder still constitutes the greatest endoscopic challenge and should be reserved for the most experienced operators. The rates for mortality (0.1%) and complications (3.3%), which include three common bile duct injuries (0.4%), are comparable to, if not better than, those for traditional cholecystectomy. The quality of recovery is markedly better: near absence of pain, short hospitalization, return to normal physical activity within 10 days, rapid return to work and preservation of the abdominal musculature in sportspeople. These advantages are unavailable to the 5.5% of patients for whom an intraoperative conversion to an open procedure is necessary. Their recovery is that of traditional cholecystectomy, which itself is far from being poor. The large multicentre studies, such as those carried out in France and Belgium recently, reporting 3708 cases, have reached identical conclusions. Laparoscopic cholecystectomy is set to become the gold standard for treatment of gallstones and is the first step towards surgical techniques of the 21st century which will be performed within the musculocutaneous envelope of the intact human body.


Management of recurrent gallstones.

The risk of gallstone recurrence following non-surgical treatment has been overestimated in the past for two reasons: (1) diagnosis of primary gallstone dissolution was based on oral cholecystography; and (2) gallstone recurrence was expressed as a cumulative recurrence rate. Results based on better methodologies for diagnosis of gallstones (ultrasonography) and for calculation of results (life-table analysis) have indicated that gallstones recur in about 50% of patients, and that the risk of recurrence is confined mainly to the first 5 years after dissolution. Pretreatment gallstone characteristics, but not patient characteristics, are important risk factors for gallstone recurrence. Multiple stones are more likely to recur than solitary stones, a phenomenon attributable to the presence of a potent pronucleating factor in the bile of patients with multiple stones. This observation, and the finding that NSAID administration may reduce gallstone recurrence via inhibition of mucin secretion, suggests that the nucleation defect might be a key factor in the pathogenesis of recurrent gallstones. Prophylaxis with low-dose CDCA or UDCA has proven ineffective for preventing gallstone recurrence, although it may reduce it. Since the majority of recurrent gallstones are small when first seen because of regular ultrasonographic follow-up, multiple, radiolucent and in functioning gallbladders, they are amenable to bile acid retreatment, and intermittent bile acid therapy is probably a viable strategy for long-term management of cholesterol cholelithiasis.


Surgical interventions for bile duct stones.

Based on our experience of 420 common bile duct procedures for stone disease and a literature review, it is evident that treatment of common duct stones today is based on a wide variety of non-operative and surgical methods which are still being developed. The mode of treatment is basically related to the time of diagnosis. Methods also differ depending on the localization of calculi, on inflammatory complications of stone disease, and whether combined or isolated cholecystocholedocholithiasis is present. At the moment, traditional operative methods as well as newly developed advanced techniques have to be evaluated. Selection of patients and their appropriate surgical and non-surgical treatment is an important issue to be further developed in the next few years. Therefore, therapeutic indications and definitive therapy present a much more demanding challenge for the surgeon than in the period when only open surgery was available.


Tumor-specific antigens revisited: presentation to the immune system of fusion peptides resulting solely from tumor-specific chromosomal translocations.

Adaptive immune responses depend upon recognition by lymphocytes-T of short polypeptide sequences bound to major histocompatibility complex (MHC) molecules. Since endogenous intracellular proteins can be presented to the immune system in this way, any tumor-specific structure may function as a potentially tumor-specific antigen. Fusion proteins arising as a result of chromosomal translocations provide good candidates for novel tumor-specific antigens recognizable by the host immune system. Recent molecular cloning data have demonstrated the existence of mRNAs encoding several different potential tumor-specific fusion proteins in both acute and chronic leukemias, and analysis of a number of these sequences suggests the presence of a newly defined amino acid motif associated with MHC-binding and T cell recognition. Preliminary data suggest the possibility of generating in vitro lymphocyte-T responses to synthetic peptides representing the chimeric sequences. It remains to be seen whether tumor cells themselves can be recognized by lymphocytes-T in vitro and in vivo, and, if so, how leukemia cells escape such immune surveillance in vivo.


The role of immune effector cells in flavone acetic acid-induced injury to tumor cells in EMT6 spheroids.

Inhibition of tumor blood flow appears to a major antitumor mechanism of flavone acetic acid (FAA), although non-ischemic processes may also be a significant role. To distinguish between direct and immune effector cell-mediated cytotoxicity as the basis for non-ischemic killing, effects of FAA were compared in EMT6 spheroids grown entirely in vitro and spheroids recovered from the peritoneal cavities of mice after six days of in vivo growth (ex vivo spheroids). Approximately 50% of the cells in the latter case were of host origin (macrophages and lymphocytes). Ex vivo spheroids showed specific histological changes when exposed to FAA, including tumor cell rounding, apoptosis, depression of mitotic activity and dissolution of necrotic debris in the spheroid core. Quantitation of histological changes indicated these effects to be significantly greater in ex vivo than in vitro spheroids. The histological changes in FAA treated ex vivo spheroids were partially inhibited by dexamethasone. Oxygen tension did not influence the response of spheroids to FAA. The results suggest that immune effector cells, probably macrophages, mediate blood flow-independent antitumor effects of FAA.


Status of the p53 tumor suppressor gene in human squamous carcinoma cell lines.

Dominant-negative and/or loss-of-function mutations of the p53 tumor suppressor gene are frequently found in squamous cell carcinomas of the skin and of the head-and-neck region. In order to identify the precise mechanisms of inactivation of p53 in tumors of this class, we examined the status of p53 RNA, protein and DNA in a panel of eight human squamous carcinoma cell lines (head-and-neck, 3; esophagus, 1; lung, 1; uterine cervix, 2; vulva, 1). Three lines (A253, CaLu-1, SqCC/Y1) failed to express any p53 mRNA. A253 cells contained a single p53 allele without mutations in exons 2-9, suggesting that the lack of transcription was the result of mutations in the regulatory region of the gene. Both p53 alleles were deleted in CaLu-1 cells, whereas the single allele present in SqCC/Y1 cells was rearranged and carried two missense mutations in exon 5. Two cell lines (A431, FaDu) expressed only 50% of the normal level of p53 mRNA, either because only one allele was present (A431), or because only one of the two alleles was transcribed (FaDu). The two cervical carcinoma lines (CaSki, C4-1) expressed normal levels of p53 mRNA, but no wild type protein, presumably as a result of accelerated degradation by the human papillomavirus 16 or -18 E6 oncoprotein present in these cells as previously described (Scheffner et al., Proc. Natl. Acad. Sci. USA 88:5523-5527; 1991). Three of the lines expressed only mutant p53 protein (A431, FaDu, CE-48) resulting from missense mutations in codons 248 and 273.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanism of prevention of development of N-nitrosobis(2-oxopropyl)amine induced pancreatic carcinoma by a protein-free diet in hamsters.

It has been shown that feeding a protein-free diet prior to injection of N-nitrosobis(2-oxopropyl)amine (BOP) can inhibit the development of pancreatic carcinoma in the hamster. The purpose of this study was to determine whether this inhibition is due to a direct effect on the pancreas or to a systemic mechanism. Pancreas transplantation was used to create four groups of two-pancreas hamsters (Group 1: protein-containing diet donor/protein-containing diet host; Group 2: protein-containing diet donor/protein-free diet host; Group 3: protein-free diet donor/protein-containing diet host; Group 4: protein-free diet donor/protein-free diet host). Animals were fed either a protein-containing diet or a protein-free diet for four weeks preoperatively. One day after transplantation, the two-pancreas animals received a 40 mg/kg body weight, subcutaneous, single dose of BOP. Animals in all groups were maintained on a regular protein-containing diet postoperatively, and were then sacrificed 42 weeks after BOP injection. The results showed that a) the incidence of carcinoma in groups 2, 3, and 4 was significantly lower than that in group 1; b) there was no significant difference in group 2 between donor and host pancreas; c) the incidence of carcinoma in the donor pancreas was lower than that in the host pancreas in groups 3 and 4. These results confirm that the protein-free diet significantly inhibits the development of BOP induced pancreatic carcinoma in the hamster. The inhibitory effect appears to act both directly on the pancreas and through an indirect systemic mechanism.(ABSTRACT TRUNCATED AT 250 WORDS)


[To break the isolation. Telecommunication to help the schooling of sick children].

A 2-way teleconferencing system has been described which links the sterile and pediatric units of the Center for Cancer Treatment in Lyon to a secondary school and the pediatric unit of the University Hospital Edouard Herriot where primary teaching is given. The Léon Bérard Center and Edouard Herriot Hospital are 300 m apart. Elie Vignal secondary school is 6 km from the first site; all three establishments are connected via hyperfrequency aerials. With the help of this system, communication (voice and image) between children in hospital and pupils or teachers in school is instantaneous. Children in bed can listen to the lesson, break in on the conversation in school, ask questions or answer those of teachers and play with children in the classroom. The aims of the system are: 1) to improve the education delivered to children and teenagers who have to spend long periods in hospital; 2) to establish a relationship between the worlds of healthy and sick children through teaching and playing in common; 3) to facilitate the social insertion of sick children after leaving the hospital.


[A new marker of aggressivity of breast cancers: loss of heterozygote on chromosome 7q].

The etiology of breast cancer is a complex interplay of various factors, including genetic alterations. A number of studies have been made to identify and characterize mutations that frequently occur during breast tumorigenesis. In this paper, we have described a new deletion, located on the long arm of chromosome 7. Patients whose tumor carried a deletion on chromosome 7q had a significantly shorter survival time. These findings identify the long arm of chromosome 7 as a candidate region for a putative tumor (or metastasis) suppressor gene.


[Hodgkin's disease associated with HIV infection: clinical characteristics and development. French registry of tumors associated with HIV infection].

From May 1987 to July 1990, 45 cases of Hodgkin's disease (HD) were recorded by the French Registry of HIV-associated tumors. Thirty-nine patients were male and median age was 30 years. Twenty-two cases had mixed cellularity type (MC), 18 nodular sclerosis, two lymphocyte depletion and three were not classified. Thirty-four patients had advanced HD clinical stages (CS III and IV). Thirty-six patients (80%) presented with B symptoms. Bone marrow involvement was diagnosed in 12 patients. Mediastinal involvement was present in only 4/30 patients (12%). Risk groups for AIDS were homosexuality in 18 cases, intravenous drug abuse in 17, both in one, and other in nine cases. In 40 cases (89%), HD occurred before any AIDS-related episode. Median CD4 cell count at HD diagnosis was 304 cells/microliters. Seventy-nine percent of the patients achieved complete remission with standard therapy, but hematological and infectious complications were very frequent. The rate of progression to AIDS was 71% at three years and opportunistic infections (mainly pneumocystis carinii pneumonia) were the most frequent cause of death. Overall two-year survival was 41% (78% for patients with initial CD4 cell count higher than 300 cell/microliters and 0% for those with CD4 cell count lower than 300/microliters). HD-HIV has a specific clinical profile as compared to primary HD, with a predominance of MC type and advanced clinical stage, without mediastinal involvement (88%). This study provides a basis for future clinical trials on HD-HIV: intensity of chemotherapy should be adapted to CD4 cell count; pneumocystis carinii prophylaxis is mandatory in all cases. Zidovudine should be included during and after HD treatment; the potential role of hematological growth factors has still to be evaluated.


[Neoadjuvant chemotherapy, with mitoxantrone, cyclophosphamide and fluorouracil, in operable breast cancer of intermediate stage: first results of a phase II study in 40 patients].

Forty patients with intermediate stage (T2 > 3 cm-T3, N0-N1) operable breast cancer received neoadjuvant chemotherapy by MCF (mitoxantrone, cyclophosphamide, 5-fluorouracil). Four cycles were administered at 3-week intervals. The obvious hematological toxicity (64% of grade III for the leucocytes and up to 34% of grade IV for the granulocytes) was rapidly reversible and did not hinder completion of the treatment. Ten patients showed a complete remission and a tumor volume regression of more than 50% was observed in 12 other patients. Tumor shrinkage allowed breast-saving surgery in 50% of the cases. A complete sterilisation of the surgical specimen was found in only two of the 40 patients and a few persisting neoplastic cells were found in ten other cases. A positive response at the level of the axillary lymph nodes was also obtained in more than 50% of the cases. In 25 of the 36 cases examined, the primary chemotherapy induced cellular lesions (fibrosis, necrosis) at the tumor level. A feasibility study was undertaken in order to determine quantitatively several biochemical parameters (steroid hormone receptors, cathepsin D, c-erbB-2 oncoprotein) in very small tumor samples obtained by Tru-Cut before any treatment and in surgical specimens. In the future, these micromethods will be used systematically with the aim of estimating the value of these potential prognostic factors for therapeutic follow-up of the patients.


In vitro characteristics of Yersinia pseudotuberculosis of nonhuman primate origin.

Six strains of serotypes 1 or 2 of Y. pseudotuberculosis were isolated from dead squirrel monkeys, a cotton-top tamarin and a marmoset hybrid. All strains harboured a 71.6 kb plasmid, all were totally oxacillin-resistant and partially resistant to cephalosporins. Biochemically, serotypes 1 and 2 differed from each other in their beta-galactosidase production in a nonfermenter system, whereas the lack of rhamnose, maltose, salicin and trehalose fermentation seemed to be attributable to technical causes.


A CAMP-like phenomenon in Serpulina (Treponema) spp.

A CAMP-like phenomenon was observed in 40 Serpulina (Treponema) isolates from the intestines of pigs, dogs, mice and rats. The strains examined included reference strains of the serotypes 1-4 of Serpulina (Treponema) hyodysenteriae and Serpulina (Treponema) innocens. The possible pathogenic importance of this phenomenon is discussed.


The chemiluminescent detection of leptospiral antigen.

The aim of this study was to investigate the feasibility of using enhanced chemiluminescence for the rapid detection of leptospiral antigen (L. interrogans serovar hardjo) in biological fluids, and to assess the suitability of such an assay for the early diagnosis of human leptospiral infections. The limit of detection for homologous antigen in phosphate buffered saline was 9 x 10(4) leptospires/ml. In human blood the sensitivity remained unchanged throughout the sampling time, (1.8 x 10(5) leptospires/ml), but decreased with time in human urine. The assay did not cross-react with other members of the Leptospira interrogans species, was unaffected by the presence of biological fluids but the sensitivity was reduced by contaminating bacteria. The assay was both rapid and sensitive, when compared with current cultural techniques, and offers a potentially valuable aid to the early diagnosis of leptospirosis.


Characterization of methicillin-susceptible and methicillin-resistant Staphylococcus aureus isolates by molecular typing methods.

Two groups of clinical Staphylococcus aureus isolates were examined by molecular typing methods. Detailed protocols for the technical procedures are described. By means of plasmid DNA profiles, plasmid DNA restriction enzyme digestion, as well as whole-cell DNA endonuclease digestions subjected to conventional agarose gel electrophoresis and pulsed-field gel electrophoresis, eight methicillin-susceptible S. aureus strains from three patients segregated into three different groups. Consecutive isolates from the same patient revealed identical fingerprints. Generally, good agreement between different molecular typing methods also was achieved in the investigation of 28 methicillin-resistant isolates. However, compared to whole-cell DNA restriction endonuclease analysis, plasmid DNA profiling (all but one strain had detectable plasmid DNA) showed a somewhat greater discriminatory ability. The techniques evaluated were reproducible and relatively easy to perform and provided valuable tools for studying the epidemiology of S. aureus in hospitals.


The isolation of Plesiomonas shigelloides in polymicrobial septicaemia originating from the biliary tree.

The first two cases are reported in which Plesiomonas shigelloides was isolated from patients with mixed aerobic/anaerobic septicaemia originating from the biliary tree. The first patient who was previously well survived after removal of a gangrenous gallbladder. The second patient suffered from an extrahepatic cholangiocarcinoma and died of infection thus highlighting the poor prognostic outcome of P. shigelloides septicaemia in immunocompromised patients. Furthermore these cases demonstrate that P. shigelloides can be isolated from mixed infections and may act synergistically with other bacteria to produce disease.


Sialic acid as receptor of Bacteroides fragilis lectin-like adhesin.

It was observed that sialic acid and macromolecules rich in this sugar were able to inhibit the hemagglutination activity (HA) of Bacteroides fragilis strains in low concentrations. Reversion of the HA and also of the adsorption to beads of Sepharose coupled to bovine submaxillary mucin, by this sugar residue corroborated the recognition capacity of the bacterial lectin-like adhesin. However, when erythrocytes were treated with clostridial neuraminidase, an increase in the HA of some strains was observed. Protease treatment of erythrocytes abolished the HA, indicating that cell receptors of B. fragilis are probably a glycoprotein moiety.


Thymocyte proliferation and maturation in response to staphylococcal lipoteichoic acid.

Lipoteichoic acid (LTA) from Staphylococcus saprophyticus strain S1 could be shown to induce thymocyte proliferation and maturation in BALB/c-mice after systemic administration. The increase in thymocyte numbers per mg organ weight was statistically significant. Determination of thymic lymphatic subsets revealed a considerable up-regulation of mature cells expressing helper/inducer (L3T4) or cytotoxic/suppressor (Lyt-2) phenotypes. Thus administration of staphylococcal LTA obviously accelerated murine thymocyte proliferation and maturation. Counts of BALB/c-mouse peripheral blood lymphocytes (PBL) revealed no evident fluctuation within one week after LTA administration, however, statistically significant increases could be detected two weeks after treatment. The determination of activated PBL expressing IL-2 receptors suggested that injection of staphylococcal LTA apparently induced an immunostimulation since those cells were significantly enhanced within one week after LTA administration.


Propionibacterium acnes-metabolites inhibit experimental lung metastasis of murine sarcoma L-1 in BALB/c-mice.

Adhesive interactions between tumor cells and host tissue occur at several stages of metastasis. Such interactions might be inhibited by microbial metabolites resembling the binding regions of matrix molecules. Certain metabolite sequences including Gly, Asp, Arg, and Ser (GAAS) proved to be critical for cell interactions, e.g. with fibronectin. In vitro, the rosette formation of murine pulmonary cells and sarcoma L-1 cells decreased significantly in the presence of Propionibacterium acnes-metabolites rich in GAAS. In vivo, coinjection of Propionibacterium acnes-metabolites and sarcoma L-1 cells significantly inhibited the formation of lung colonies in BALB/c mice. The inhibition of lung colonization by these metabolites appeared to be noncytotoxic and obviously did not result from impairment of cellular tumorigenicity.


Trypanosoma congolense: manifestation of resistance to Berenil and Samorin in cloned trypanosomes isolated from Zambian cattle.

Four Trypanosoma congolense clones derived from a Mumbwa field isolate proved to be resistant to Berenil with a minimum curative dose (MCD) value of 40 mg/kg and to Samorin with an MCD of 4 mg/kg for mice. Two other clones, one being resistant to Berenil with an MCD of 45 mg/kg but susceptible to 1 mg/kg Samorin, and the other being resistant to Samorin with MCD of 16 mg/kg but susceptible to 7 mg/kg Berenil, were experimentally rendered resistant to each of the respective drugs they were susceptible to by subcurative treatments in mice. The original trypanosome strains and their derivative clones were then screened for their sensitivity to Berenil or Samorin. Three clones derived from the Mumbwa isolate were resistant to Berenil, with MCD's of 14 to 28 mg/kg, and to Samorin, with MCD's of 4 mg/kg. A single Mumbwa derivative clone was relatively sensitive to both Berenil with an MCD of 7 mg/kg and to Samorin with an MCD of 2 mg/kg. The reciprocal drug induction results confirmed that although trypanosomes can acquire tolerance to both Berenil and Samorin, no cross-resistance between the two was evident.


Non-pathogenic entamoeba histolytica in Italian HIV-infected homosexuals.

A cohort of 51 homosexuals who were either HIV-positive or had AIDS was followed prospectively with parasitologic stool examination and in vitro culture in order to determine the incidence of E. histolytica infection. Amoebic isolates were further characterized by electrophoretic isoenzyme study. Five subjects (9.8%) were found to be infected with E. histolytica. None of the amoebic isolates were found to be pathogenic by isoenzyme analysis.


Escherichia coli types isolated from porcine E. coli infections in Saxony from 1963 to 1990.

Between 1963 and 1990, 4221 Escherichia coli strains were isolated from 4221 cases of porcine neonatal colibacillosis and 16826 E. coli strains from 16064 cases of E. coli enterotoxicosis of weaned pigs. They belonged to serotypes which, due to their enterotoxigenicity or verotoxigenicity, are considered to be pathogenic for pigs. Nonhaemolytic enterotoxigenic strains characterized by one of the fimbrial antigens K99 (F5), 987p (F6), and F41 and one of at least 8 different A antigens were only found in suckling piglets. Haemolytic serotypes lacking the K88 (F4), K99, 987p, and F41 fimbrial antigens as well as A antigens were only isolated from pigs with E. coli enterotoxicosis of weaned pigs, which can occur already some days before weaning, while enterotoxigenic types carrying the fimbrial antigen K88 were found in both neonatal colibacillosis and E. coli enterotoxicosis of weaned pigs. In the 28 years considered, the type O149: (K91), K88 dominated in neonatal colibacillosis and, since 1972, in E. coli enterotoxicosis of weaned pigs, too. It was mainly nonhaemolytic during the first years and always haemolytic later. The emergence of type O147: (K89) coincided with a gradual disappearance of type O147: (K89), K88, both types differing in their biochemical behaviour.


Yersinia enterocolitica serovar 1,2a,3 biovar 3 in chinchillas.

Yersinia enterocolitica (serovar 1,2a, 3; biovar 3, autoagglutination test positive) was isolated in a chinchilla, in which autopsy showed the typical lesions associated with pseudotuberculosis. We assume that this "chinchilla type" of Yersinia enterocolitica still persists among stock, more than thirty years after its discovery. A brief overview of the distribution of the pathogen in Europe and North America is given.


The nuclear serine/threonine protein kinase DNA-PK.

The DNA-activated protein kinase (DNA-PK) is a nuclear serine/threonine protein kinase that phosphorylates DNA-binding proteins, including several transcription factors. DNA-PK is one of a very few enzymes known to be regulated through interaction with DNA that does not have DNA as a template or substrate. We suggest that DNA-PK may function in cell homeostasis, in part through the modulation of transcriptional activity.


Biological and functional aspects of catalytic RNAs.

Several naturally occurring ribozymes have now been well characterized with respect to their in vivo and in vitro activities. Through detailed biochemical and genetic analyses, it has become possible to alter the substrate specificity of each ribozyme using simple Watson-Crick base pairing. Several laboratories, therefore, have designed ribozymes to cleave viral or other cellular transcripts in vitro with the hope of developing these molecules as antiviral or therapeutic agents. In addition to Watson-Crick base pairing, however, other factors such as protein or RNA tertiary interactions are involved in the ribozyme cleavage activity. Although several engineered ribozymes have been used successfully to reduce gene expression in vivo, it is difficult to determine whether gene expression has been reduced by the cleaving activity of the ribozyme or by its inherent antisense activity. In order to discriminate between these two activities and optimize potentially therapeutic ribozymes, it is imperative to develop in vivo assays in which the antisense activity of ribozymes is negligible.


Initiation of replication in mammalian chromosomes.

Mammalian origins of replication are scattered at about 100-kb intervals along each chromosomal DNA fiber. It is not known whether origins are genetically defined sequences analogous to those that control initiation of replication in microorganisms. Since the advent of recombinant DNA techniques, it has become possible to search for origins in defined chromosomal domains. A variety of methods have suggested that nascent chains initiate at preferred locations on the chromosome, but there is some disagreement as to how precisely defined these initiation sites are.


Improvement in protein absorption with a small-peptide-based diet in patients with high jejunostomy.

We compared urinary and fecal excretions of fluid, electrolytes, and nutrients in six patients with a high jejunostomy during three randomized consecutive 3-day periods of total enteral nutrition with three diets differing only by the degree of hydrolysis of the protein moiety: whole proteins, their hydrolysate (63% nitrogen as small peptides with < 1000 M), and the two mixed together. Daily nitrogen absorption was significantly enhanced with the small-peptide and mixed diets (14.3 +/- 3.4 and 13.1 +/- 2 g, respectively) compared with the whole protein diet (10.9 +/- 2.4 g, p = 0.012). Concomitantly, blood urea nitrogen and urinary urea excretion increased with the small-peptide diet. Apparent absorption of fat and calories, fecal weight, and urinary and fecal excretions of sodium, potassium, calcium, and magnesium remained unchanged. We conclude that a small-peptide-based diet may be beneficial in patients with short-bowel syndrome.


Dietary L-lysine and calcium metabolism in humans.

Calcium deficiency contributes to age-related bone loss; consequently, any preventive approach to osteoporosis should include dietary Ca adjustment or supplementation. The ideal Ca supplement would yield the greatest bioavailability. Studies in animals have shown that dietary supplements with certain amino acids, particularly L-lysine, can increase Ca absorption. Therefore, we examined the potential effect of this essential amino acid on Ca metabolism in humans. In one study, the acute effects of an oral Ca load (3 g as CaCl2) administered with or without 400 mg of L-lysine were compared in 15 healthy and 15 osteoporotic women. In all cases, the oral Ca load determined a progressive increase in serum total Ca and Ca2+ and a concomitant decrease in neophrogenous cAMP. As expected, a progressive increase in urinary Ca excretion was also observed, except in the L-lysine-treated healthy subjects, who exhibited a blunted calciuric response to the Ca load. In a second study, the effects of a short-term dietary supplementation with either L-lysine, L-valine, or L-tryptophan (800 mg/day) on 47Ca fraction absorption were compared in 45 osteoporotic patients. L-Lysine but not L-valine or L-tryptophan significantly increased the intestinal absorption of the mineral. Our results suggest that L-lysine can both enhance intestinal Ca absorption and improve the renal conservation of the absorbed Ca. The combined effects may contribute to a positive Ca balance, thus suggesting a potential usefulness of L-lysine supplements for both preventive and therapeutic interventions in osteoporosis.


Diet, age and intestinal bile acids in pigs.

Total bile acid concentrations in gallbladder bile and duodenal juice of neonatal piglets receiving sow milk were compared to values from 10-wk-old pigs receiving either high-fat low-carbohydrate (HF/LC) or low-fat high-carbohydrate (LF/HC) diets. Ten-week-old pigs on either diet had higher bile acid concentrations in gallbladder bile than newborn pigs (108.6 +/- 2.5 and 109.3 +/- 1.4 vs. 50.0 +/- 10.0 mM, mean +/- SE for HF/LC, LF/HC, and newborn, respectively, p < 0.007; n = 8-10). Ten-week-old pigs in the LF/HC group had higher bile acid concentrations in duodenal juice than either the HF/LC or newborn animals (31.7 +/- 4.2 vs. 16.8 +/- 2.5 and 14.7 +/- 1.8 mM, respectively, p < 0.0001). These data demonstrate that like the human neonate, the newborn pig has decreased bile acid concentrations available for digestion compared with the adult and resembles the adult pig adapted to a high-fat diet.


Enriched feeding formula and immune responses and outcome after Listeria monocytogenes challenge in mice.

Immunocompromised malnourished patients are at high risk of developing serious opportunistic infection. This study examined the effect of feeding a special nutrient-enriched formula (Immun-Aid) on immune responses and mortality in mice challenged with Listeria monocytogenes. Two protocols were followed. In the first protocol, the animals were challenged with microorganisms when the experimental formula was introduced as the sole source of their nutrition. There was no significant effect on total T-lymphocyte number, but the proportion of helper T cells increased by day 7, resulting in a higher helper/suppressor (H/S) T lymphocyte ratio as well. Response to the mitogen phytohemagglutinin (PHA) was slightly higher on day 3 but came down and was comparable with that of control animals by day 7. Natural killer cell activity was slightly higher on day 7. Other immunologic parameters were unchanged. There was no significant difference in mortality between the two groups. In the second protocol, the animals were fed the experimental diet for 7 days before the infectious challenge. There was a slight increase in the total number of T lymphocytes on day 7. The numbers of helper and suppressor T lymphocytes were unchanged, but H/S was slightly higher on day 3 in the experimental group. Response to PHA was again higher on day 3 but plateaued on day 7. Natural killer cell activity was not altered. Mortality after infectious challenge was slightly but significantly decreased in the group of animals fed the enriched special formula. These results indicate a slight enhancement of selected parameters of immunity in mice fed the specially enriched formula and show that prior feeding with this formula for several days may partly protect against infectious challenge, resulting in reduced mortality.


Hemoglobin levels and anemia-associated symptoms in pregnant Liberian women.

An epidemiological study was conducted of 515 pregnant Liberian women. The purposes of the study were to 1) assess the prevalence of anemia in Liberian women during the last trimester of pregnancy (when latent deficiencies are more apt to become clinically manifest), 2) ascertain which physician-obtained symptoms are related to low hemoglobin (Hb) levels and anemia, and 3) determine the sensitivity and specificity of symptoms commonly associated with anemia. The results indicated that the prevalence of anemia (defined as Hb < 11.0 g/dl) was 79.8%. Women who had headache as a symptom had significantly lower mean Hb values than women who did not have this symptom. The socioeconomic status of women with and without symptoms was not statistically different. The sensitivity of headache as an indicator of anemia and low Hb values was 83%, but the specificity of this symptom was low (27%). The utility of signs and symptoms as indicators is discussed in relation to the economic means of lesser-developed societies and their cultural practices.


Fine-bore peripheral catheters versus central venous catheters for delivery of intravenous nutrition.

We present a descriptive study of 229 consecutive inpatients requiring intravenous nutrition. These patients received either complete peripheral intravenous nutrition via a fine-bore silicone catheter (n = 80) or short Teflon catheter (n = 15) or received conventional central intravenous nutrition (n = 134). Nutrient delivery was similar for both systems, providing 0.2-0.4 g N.kg-1 x day-1 and 0.13-0.15 mJ.kg-1 x day-1 from preparations containing 4.3 MJ/L total energy (65-75% lipid: 25-35% glucose for peripheral support and 100% glucose for central delivery) with 6 g N/L. We compared the incidence of catheter complication and the probability of catheter function over time for the peripheral and conventional central systems. Venous access complications were seen only with central venous catheterization (10.4%). Chemical phlebitis occurred in 17% of fine-bore catheters and 91.4% of Teflon catheters. The infective phlebitis rate of fine-bore silicone catheters was 1.02% and daily risk of phlebitis 0.016%, with no instance of device-related bacteremia or sepsis. Central-line microbial contamination (21.7%) and catheter-related sepsis (3%) were significantly greater (p < 0.0005, chi 2 goodness-of-fit test) than with fine-bore silicone and Teflon catheters. The probability of complication-free function against time was similar (0.75 < p < 0.90, log-rank test) in fine-bore silicone catheters and central venous catheters. We conclude that fine-bore silicone catheters provide long-term phlebitis-free delivery of complete peripheral intravenous nutrition.


Regulation by insulin of muscle protein metabolism during sepsis and other catabolic conditions.

The anabolic effect of insulin in skeletal muscle reflects increased protein synthesis and reduced protein degradation. Insulin stimulates protein synthesis mainly at the translational level by enhancing peptide chain initiation. The mechanism by which the hormone reduces protein breakdown is less well understood, but inhibition of the lysosomal pathway is probably an important component. Sepsis results in pronounced muscle catabolism, mainly reflecting increased protein breakdown, particularly myofibrillar protein breakdown, and a less prominent inhibition of protein synthesis. There is evidence that muscle protein breakdown becomes resistant to the effect of insulin during sepsis, probably at the postreceptor level. This insulin resistance may be mediated by increased beta-adrenoreceptor activity. In contrast, the stimulatory effect of insulin on muscle protein synthesis and amino acid transport is maintained during sepsis. The regulatory effect of insulin on muscle protein metabolism may be affected by other catabolic conditions as well, e.g., fasting, denervation, burn injury, and trauma.


[The effect of carteolol. Prolonged and increased effect by liposome suspension].

Liposomes are small lipid vesicles capable of trapping beta-blockers such as carteolol within their bilayer structure, the advantage being improved drug action, prolonged action time, and a reduction in drug concentration. In a prospective, randomized double-blind trial, carteolol 2%, liposomes (frozen and thawed multilamellar vesicles, FAT-MLVs), or carteolol 2% suspended with FAT-MLVs was applied to 25 eyes of 25 patients per group in a single 20 microliters dose. Intraocular pressure was measured for 3 days. A significant reduction in the IOP was observed in the patient groups receiving carteolol and carteolol suspended with liposomes. Moreover, improved action and prolongation of drug action was noted in the carteolol/MLV group as compared to carteolol treatment alone. Hence, carteolol 2% is suitable for reduction of IOP, but a reduction of drug concentration can be achieved by suspension with liposomes, thus reducing the side effects.


[Does timolol modify retinal hemodynamics in patients with normal pressure glaucoma?].

In 31 patients with normal-pressure glaucoma, retinal blood flow, diameter of the retinal vessels and velocity were measured with 2-point fluorometry and automatic measurement of the diameters before and after administration of 0.5% timolol over 2 weeks. After timolol therapy the tension was significantly decreased (before therapy: 18.26 +/- 2.50; after therapy: 15.61 +/- 2.56 mm Hg, P < or = 0.01). The arterial and venous diameters and blood flow were nearly unchanged, but a slight increase in the arterial and venous velocity was noted. We conclude that timolol does not significantly influence the retinal hemodynamics in patients with normal-pressure glaucoma.


[Removal of silicone oil in treatment of so-called emulsification glaucoma].

We investigated whether emulsification glaucoma after silicone oil implantation can be influenced positively by removal of the oil. In 16 of 264 patients successfully operated upon with purified silicone oil 5000 cps, we found a glaucoma refractory to medical therapy and probably caused by emulsification. We removed the silicone oil from these eyes and followed them up for a period of 6 months (12.5 +/- 7.3 months). In 12 of the 16 eyes, the intraocular pressures were normalized after silicone oil removal with or without antiglaucomatous therapy. Four eyes showed raised intraocular pressures in spite of silicone oil removal. These could, however, be largely explained by neovascularization or chronic inflammation with increasing anterior synechia formation. In eyes with possible emulsification glaucoma, early and thorough removal of the silicone oil is therefore recommended since this can result in normalization of intraocular pressures in a large percentage of cases.


[1,3,7-trimethylxanthine. Effects on circadian aqueous humor dynamics in probands].

Anterior chamber fluorophotometry (Fluorotron Master II, Coherent, Palo Alto, Calif.) was used to investigate the influence of 1,3,7-trimethylxanthin on the circadian rhythm of aqueous humor secretion in two age-, race- and sex-matched groups of healthy volunteers. In ten males and ten females (mean age 27 years), aqueous humor secretion was measured over 24 h at: 0800, 0900, 1000-1400, 1500, 1600-2000, 2100, 2200-0200, 0300, and 0400 hours. Flow was calculated using the Yablonsky protocol of Fluorotron Master II. In group I all volunteers received about 800 mg trimethylxanthin in the form of caffeinated coffee between 2200 and 2300 hours. In group II volunteers went to sleep at 2300 hours. Sleep was only interrupted for measurements. During the daytime the mean aqueous humor flow was the same in both groups (0800 to 2200 hours) (Student's t-test): Group I (n = 10) RA 2.27 +/- 0.70 microliters/min LA 2.25 +/- 0.74 microliters/min Group II (n = 10) RA 2.23 +/- 0.73 microliters/min LA 2.06 +/- 0.64 microliters/min During the night the mean aqueous humor flow decreased in both groups (0200 to 0400 hours): Group I: RA 1.99 +/- 0.74 microliters/min delta flow = -12% LA 1.93 +/- 0.75 microliters/min Group II: RA 0.97 +/- 0.50 microliters/min delta flow = -56% LA 0.97 +/- 0.48 microliters/min The difference between groups was statistically significant (P = 0.01, t-test for unpaired samples). There was no significant change in mean aqueous humor flow between the daytime vs night in group I (P < 0.5).(ABSTRACT TRUNCATED AT 250 WORDS)


[Inner nuclear layer of the retina in eyes with secondary angle-block glaucoma].

Glaucomatous changes have been known to occur in the inner retinal layer all over the fundus and in the deep retinal layer and retinal pigment epithelium close at the optic disc border. This study was conducted to address the question as to whether the middle retinal layers are altered by the glaucomatous process. The study included histological slides of 23 eyes enucleated due to painful secondary traumatic angle-closure glaucoma and 14 nonglaucomatous eyes removed because of a malignant choroidal melanoma. We evaluated the cell count and thickness of the inner nuclear layer via histomorphometry. The inner nuclear layer contained significantly fewer cells and was thinner (P < 0.05) in the glaucoma group compared to the control group. Since this study contains eyes with possible secondary changes due to the initial trauma, further investigations on eyes with primary open-angle glaucoma are necessary to confirm the results. This could be important for psychophysical testing in glaucoma.


[Visual acuity perimetry. Detection of glaucomatous visual field defects].

50 eyes of 50 patients with different types of glaucoma (27 eyes with POAG, 14 eyes with glaucoma due to pseudoexfoliation, 8 eyes with chronic narrow-angle glaucoma, 1 eye with normal-tension glaucoma) were examined with light-sense perimetry (Humphrey-Field-Analyzer, program 30-2) and resolution perimetry according to Frisén [2-7]. As the field area tested by Frisén's ring perimeter is smaller than that of the HFA, the comparison was restricted to the area of the ring perimeter, so that 50 out of 77 test locations of the HFA were included. In addition to a quantitative comparison with statistical criteria based on age-corrected normal values, a subjective qualitative assessment was established. The quantitative comparison of all hemifields showed good agreement in 61% of eyes, the ring perimeter indicating moderately and markedly increased numbers of defects in 13% and 4% of eyes and the HFA in 18% and 4% of eyes, respectively. Qualitative comparison of the entire fields revealed good agreement in 46% of eyes, with moderately and markedly more defects in 18% and 10% for the ring perimeter and 12% and 14% for the HFA, respectively. The average time needed for examination was 6.0 +/- 1.1 min for the ring perimeter and 17.2 +/- 2.7 min for the HFA. The Global Deviation of the ring perimeter correlates linearly with the Mean Deviation of the HFA (r = 0.4824, P < 0.001).


[White-noise field campimetry before and after artificial increase of intraocular pressure. Possible applications in diagnosis and evaluation of glaucoma].

A total of 173 eyes (visual field defect stages O-V) of 99 glaucoma patients were investigated by means of conventional threshold-oriented suprathreshold automated test point perimetry using the Tübingen Automatic Perimeter (TAP) and by means of white-noise-field campimetry (flickering random dot pattern) using the Tübingen Electronic Campimeter (TEC). Most eyes were affected by primary open-angle glaucoma (119) or low tension glaucoma (35). The concordance between the two methods was good in 65 eyes (37.6%). Sufficient in 32 (18.5%) eyes, poor in 32 cases (18.5%) and inadequate in 44 eyes (25.4%). Among the last group of 44 eyes, 32 perceived a scotoma in the noise field (NF) but did not show any pathologic defect in conventional automated test point perimetry: the opposite constellation was found in only 12 eyes. In most cases, scotoma in the NF showed a change in both brightness and motion (noise) perception. No clear relationship between the type of glaucoma and a certain constellation of the aforementioned NF specifications could be found. Complete lack of noise perception in the scotoma occurred more frequently in advanced glaucoma (stage > or = IV). In 110 eyes of 63 of the glaucoma patients, white-noise-field campimetry was carried out during artificial IOP elevation achieved by suction-cup oculopression: during steplike increases of the negative pressure in the suction-cup up to maximum of 375 mmHg the following stages could be seen (the percentage of eyes that perceived each phenomena over the negative pressure range is shown in brackets): change in NF perception compared with initial findings (96.4%); impairment of central noise-field perception (78.2%); concentric constriction of NF (61.8%); complete breakdown of noise (field) perception (42.7%). A further, quantitative classification of these eyes was possible by evaluation of the negative pressure in the suction-cup that led to any one of these NF phenomena. The results demonstrate the usefulness of white-noise-field campimetry as a very fast screening method for detecting glaucomatous visual field defects. It can also be performed as a pressure tolerance test and thus be used to classify glaucomatous risk stages.


[2 years self-tonometry. Acceptance and results].

For more than 2 years we have been trying out a microprocessor-controlled self-tonometer to determine its clinical usefulness. Most of the measurements were taken with two instruments (A and B). In vitro calibration series on human donor corneas gave good results over the whole pressure range. In a patient series both instruments were compared with the established hand-held applanation tonometer put out by Draeger (HAT). Each self-tonometer was applied three times, followed by a controlling measurement with the HAT. The correlation coefficient between instrument A and HAT was 0.85 with a standard deviation of +/- 1.9126 mmHg. Instrument B showed a better correlation (r = 0.904), the standard deviation was similar to tonometer A (SD = +/- 1.8598 mmHg). Most of the values obtained by the self-tonometers-about 50%-deviated from the corresponding HAT values by +/- 1 mmHg. The new measurement principle was accepted by 75% of all patients. Improvements in the details are planned in order to simplify tonometer handling and increase the accuracy and precision of the measurements.