Long-term neurological sequelae after decompression sickness in retired professional divers.

INTRODUCTION: Decompression sickness (DCS) has traditionally been categorized as type I DCS, affecting joints and skin, and type II affecting the nervous system. In the present study, we wanted to examine whether divers with a history of neurological DCS demonstrated a pattern of symptoms and clinical neurological and neurophysiological signs different from divers with other manifestations of DCS or no history of DCS. METHODS: Up to 1990, 365 Norwegian offshore divers worked in the North Sea. Two hundred and eight divers who had performed saturation diving, bounce diving or both, were included in this study. They filled in a questionnaire for registration of diving experience and health complaints, and episodes of DCS were registered. All participants had a clinical neurological and neurophysiological examination (ERP- P300). RESULTS: One hundred and sixty three of the 208 divers (78.4%) reported episodes of DCS. Neurological DCS was reported by 41 (19.7%) divers. Forty-five divers (21.6%) reported no episodes of DCS. Divers who reported episodes of DCS reported significantly more symptoms compared with divers who reported no DCS. Divers who reported neurological DCS had significantly more neurological findings on motility tests, sensory tests and coordination/cerebellar tests. The P300 motor reaction times were significantly longer in divers reporting DCS, but there was no significant difference between divers with neurological DCS and divers with other forms of DCS. CONCLUSIONS: This study indicates that DCS is associated with long-term effects on the nervous system independent of the symptomatology in the acute stage.

Electroencephalography and magnetic resonance imaging in neurological decompression sickness.

The purpose of this study was to evaluate the use of electroencephalography (EEG) and magnetic resonance imaging (MRI) in the clinical evaluation of acute decompression sickness (DCS) in the central nervous system (CNS). Twenty-one patients treated because of acute DCS in the CNS during 1999-2001 were included, 15 patients with clinical cerebral DCS and five with clinical spinal cord DCS. Seven patients had abnormalities in their EEG, five with cerebral DCS and two with spinal cord DCS. MRI showed high intensity lesions in the spinal cord in four patients with clinical spinal cord DCS and in one with clinical cerebral DCS. Cerebral lesions were not identified by MRI in any patient. In conclusion, EEG showed unspecific abnormalities in only one third of the cases. Conventional MRI with a 1.5 T scanner may be of help in the diagnosis of DCS in the spinal cord, but not in the brain. EEG and MRI have low sensitivity in the diagnosis of acute DCS in the CNS. Recompression treatment of DCS should still be guided by clinical neurological examination and assessment of symptoms.

Thymopentin prophylactic treatment in patients with recurrent respiratory infections.

Present immunological methods do not regularly detect abnormalities in patients with chronic bronchitis, and no single parameter appears to be closely associated with the clinical findings. Of the many tests performed in the cited studies, the Merieux multitest procedure seems to offer the best findings in further studies, followed by determination of the OKT4/OKT8 ratio. The theoretical background for the use of an immunologic approach to prevent frequent recurrences of infections is discussed in depth, with particular emphasis on the pharmacologic efficacy profile of thymopentin. The safety of this drug is remarkably unproblematic. The present survey of 11 clinical studies shows that thymopentin treatment reduces the incidence of recurrent respiratory tract infections. The most frequently used dosing regimen is 50 mg SC three times a week for 6 weeks, which may be repeated after 3-6 months. The clinical effect appears long-lasting, ie, 3-4 months after discontinuation of treatment.

Thymopentin treatment of rheumatoid arthritis.

Although the etiology of rheumatoid arthritis (RA) is unknown, there is solid evidence that immunological factors play a pivotal role in its pathogenesis. It seems that a hyporeactivity of local (intraarticular) T-suppressor cells would permit an excessive immune response that ultimately leads to the classical symptoms and signs of inflammation and cartilage damage. Thymopentin is a synthetic pentapeptide (Arg-Lys-Asp-Val-Tyr) which represents the active biologic site (sequence 32-36) of the native thymic hormone thymopoietin, containing 49 amino acids. Thymopoietin and thymopentin have been shown to possess immuno-normalizing properties in a number of animal model systems. Low concentrations of the hormone characteristically stimulate the OKT4-positive cells, whereas higher concentrations additionally induce stimulation of OKT8-positive cells. This report summarizes the clinical experience collected by Italian investigators, and discusses the results with a view to previously published papers.

Management of viral infections with thymopentin.

Recurrent herpes simplex-, herpes zoster- and human papilloma virus infections are sometimes difficult to control by traditional antiviral therapy. Although detectable immune disturbances are not regularly associated with the clinical presentation, a compromised cellular immunity has been found to play an important role in the pathogenesis of those diseases. Thymopentin (Arg-Lys-Asp-Val-Tyr) is a synthetic pentapeptide corresponding to the active structure of the natural 49 amino acids containing thymic hormone thymopoietin, which has shown impressive immunoregulatory activity in many animal model systems and human in-vitro tests. Cumulative clinical experience with this drug has suggested that it would be of particular value in certain recurrent viral diseases. This report summarizes some of the individual studies performed so far, and discusses the mechanisms of action within the context of relevant published articles in this field. Contrary to antiviral drugs, thymopentin's effect appears to be long-lasting also after discontinuation of treatment. The drug seems to be extremely safe and no serious adverse reactions have been reported to date.

Correction of anaemia of chronic renal failure with recombinant human erythropoietin: safety and efficacy of one year's treatment in a European multicentre study of 150 haemodialysis-dependent patients.

One hundred and fifty patients undergoing regular haemodialysis for end-stage renal failure entered a trial of treatment for anaemia with recombinant human erythropoietin (r-HuEPO). At data cut-off 37 patients (24.6%) had dropped out for various reasons; most of them (n = 22) discontinued because of kidney transplantation (after 3-17 months of treatment). The initial dose was 24 U/kg i.v. thrice weekly, with subsequent dose escalations after a minimum of 2 weeks if the haemoglobin (Hb) was less than 10% above the pretreatment baseline. One hundred and forty-three patients who were eligible for efficacy analysis achieved an Hb increase of greater than or equal to 2 g/dl, and all 139 patients eligible for 'full response' analysis (Hb between 10 and 12 g/dl) were dose titrated to reach this arbitrarily defined optimal range. Patients' response to r-HuEPO treatment was independent of age, weight, nephric state or duration of dialysis treatment. To maintain the Hb within the range of 10-12 g/dl during 1 year's treatment (n = 96) a median weekly r-HuEPO dose of 200 U/kg (range 150-300) divided into one, two, or three administrations appeared to be adequate. This maintenance dose depends slightly on the patient's baseline Hb. The study provides evidence that long-term treatment with r-HuEPO is safe. In 48 patients (of whom 12 had no history of hypertension) elevation of blood pressure required additional treatment, which was effective in all but one who was withdrawn from the study. Four patients had seizures and one suffered hypertensive encephalopathy without convulsions.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of transfusion-dependent anaemia of chronic renal failure with recombinant human erythropoietin. A European multicentre study in 142 patients to define dose regimen and safety profile.

This multicentre study in 142 transfusion-dependent patients with chronic renal failure maintained by haemodialysis was performed to establish the appropriate dose regimen of rHuEpo and define its long-term safety profile. Only one of 132 patients eligible for efficacy analysis did not achieve the haemoglobin target of greater than or equal to 10 g/dl; this particular patient had folate deficiency and overt hyperparathyroidism. Regular blood transfusions were no longer necessary in any patients, however five patients needed blood transfusions only once, not due to rHuEpo failure: two for iron deficiency and three for intercurrent disease. In parallel with the haemoglobin increase a statistically significant improvement in quality of life scores was observed. The weekly dose required to maintain median haemoglobin between 10 and 10.5 g/dl for 1 year (n = 79) was 200-225 U/kg, applied as two or three i.v. injections. Mean serum ferritin decreased from 1900 to 1300 ng/ml and transferrin saturation from 60% to 30%; this feature was associated with statistically significant decrease of pre-study elevated liver enzymes. The treatment had no untoward effect on the outcome of renal transplantation (n = 24). Of the 56 patients who experienced hypertensive episodes during rHuEpo therapy, 47 had a history of hypertension and nine had not. The patient incidence during the first 3 months was 28.9% and fell markedly to 4% after 1 year. Only two hypertensive episodes could not be controlled and the patients dropped out. Seizures occurred in 11 patients, most of them during early treatment; annualised incidence during the first 3 months was 7.78 per year vs 2.07 per year for seizures beyond 3 months treatment. Clinical presentation, patients' history, haemoglobin pattern, BP recordings, brain scan, and EEG indicated that the pathophysiology is multifactorial, with emphasis on rate of haemoglobin increase. Therefore a smooth haemoglobin increase rate, induced by a conservative starting dose regimen (50 U/kg thrice weekly) is recommended, to allow the circulation to adapt to changes in haematocrit/viscosity and O2 delivery. The majority of the observed adverse reactions were related to rHuEpo's therapeutic effect, i.e. increase the haematocrit. The side-effects are therefore largely predictable and can be successfully managed.

[Allergic reaction to meningococcal antigen. Clinical aspects, pathogenesis and diagnosis related to a case history]. / Die allergische Reaktion auf das Meningokokken-Antigen Klinik, Pathogenese und Diagnostik anhand einer Fallbeschreibung.

A case report illustrates a complication of meningococcal meningitis which often causes differential-diagnostic problems: allergic reaction to the meningococcal antigen. The pathogenesis and diagnostic principles are discussed in the light of the literature.

[Herpes simplex encephalitis. A case report with support of the diagnosis by means of brain biopsy]. / Herpes-simplex-Enzephalitis Eine Fallbeschreibung mit Sicherung der Diagnose durch Hirnbiopsie

The pathogenesis, differential diagnosis and therapeutic problems of herpes simplex encephalitis are discussed. Early diagosis of herpes simplex as a leading, and possibly the sole, cause of acute necrotizing encephalitis is crucial to effective management. Decompressive craniotomy in the presence of fulminating cerebral swelling associated with acute onset of the disease is of value as an adjuvant to definitive therapy with antiviral agents.

[Gonorrhoic perihepatitis. Fitz-Hugh-Curtis syndrome]. / Perihepatitis gonorrhoica. Fitz-Hugh--Curtis--Syndrom.

The Fitz-Hugh--Curtis syndrome is an extragenital manifestation of gonorrhea, characterized by fibrinous inflammation of the subphrenic area with violinstring-like adhesions between the liver surface and the parietal peritoneum. When such patients present with acute upper right quadrant pain, the differential diagnosis to other abdominal emergencies (cholecystitis, peptic ulcer disease etc.) may be difficult, because it will not always be possible to isolate the causative agent from the external genitals. In such cases only a laparoscopic approach will allow a correct diagnosis. Two case reports are discussed in the light of the literature.

Clinical experience and results of treatment with suprofen in pediatrics. 2nd communication: Use of suprofen suppositories as an antipyretic in children with fever due to acute infections/A single-blind controlled study of suprofen versus paracetamol.

The present randomized single-blind trial was performed to study antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol) suppositories versus paracetamol (acetaminophen) suppositories in pediatric patients with fever of various etiology. The study included a population of 120 patients ranging in age from 2 to 12 years; the subjects' mean rectal temperature was 39.3 degrees C in the beginning of the therapy. The dosage of the suppositories depended upon body weight; medication was applied up to 3 times a day. The temperatures were recorded 0.5, 1, 1.5, 2, 3, 4, 5, and 6 h after the preparation was first applied. Pulse rates and respiratory rates were measured at the same rating times. The antipyretic effect of suprofen in younger patients was from 1 through 6 h (except at 3 h) statistically significantly superior to that of paracetamol. In older children, the differences in favor of suprofen were statistically significant only at 1 and 2 h after application of the drug. After the treatment pulse and respiratory rate dropped in both age groups on either treatment. The means were within the normal range at all rating times. The only adverse reaction was vomiting; this phenomenon occurred in 4 cases, i.e., in 2 cases each on either drug.

Clinical experience and results of treatment with suprofen in pediatrics. 3rd communication: Antipyretic effect and tolerability of repeat doses of suprofen and paracetamol syrup in hospitalized children/A single-blind study.

Antipyretic effect and tolerability of alpha-methyl-4-(2-thienylcarbonyl)-phenyl acetic acid (suprofen, Suprol), syrup and paracetamol (acetaminophen) were compared within the scope of the present randomized single-blind study; the test population included a total of 115 children ranging in age from 6 months to 12 years. All patients were admitted to the hospital with an average temperature of 39.3 degrees C, their disease being caused by bacterial or viral infections. The dose levels for treatment with syrup depended upon the children's age and body weight. Treatment was in most cases given for two days; a three-times-a-day schedule was used. The (rectal) temperature as well as pulse and respiratory rates were measured prior to treatment and 0.5, 1, 1.5, 2, 3, 4, 5, 6 h after first administration of the test preparations. The results showed that the antipyretic effect of suprofen was in both age groups at all rating times statistically significantly superior to that of paracetamol. Pulse and respiratory rates dropped in both age groups after treatment; the means were within the normal range at all rating times. Adverse drug reactions were seen in 5 patients on suprofen and in 3 cases on paracetamol. It is, however, questionable whether such reactions are drug-dependent.

Thymopentin treatment in patients with chemotherapy-resistant lepromatous leprosy.

Leprosy is a chronic infectious disease caused by Mycobacterium leprae; it is chiefly involving the skin and peripheral nerves. In lepromatous leprosy there are widespread loose infiltrates with M. leprae multiplying extensively in the skin macrophages and Schwann cells of peripheral nerves. Such patients reveal a decrease of circulating T helper cells, which is still more pronounced in the cutaneous lesions. Due to the ever increasing bacterial resistance to classical dapsone and combined chemotherapy as well, an immunomodulatory approach seemed reasonable: Eight patients with long-lasting (5-40 years) disease who had become resistant to combined chemotherapy were treated with thymopentin, 50 mg s.c., 3 times weekly for 5 weeks and thereafter combined with dapsone and clofazimine for 5 months. During the trial a statistically significant increase in E-rosette-forming cells (p less than 0.05) was observed, along with a steady improvement of the bacterial status of the nasal mucus. Although the skin lesions did not disappear within the observation period of the study, it is important to realize that long-term improvement of such lesions is always initiated by clearance of bacilli from the nasal mucus, hence, thymopentin treatment appears to be a promising approach to chemotherapy-resistant lepromatous lepra.

Effect of low and moderate doses of recombinant human erythropoietin on the haematological response in premature infants on a high protein and iron intake.

UNLABELLED: There is no consensus regarding protein intake and the doses of recombinant human erythropoietin (r-HuEpo) and iron in the treatment of anaemia of prematurity (AOP). This open, randomized study has compared the effectiveness of 50 IU r-HuEpo/kg with that of 100 IU/kg, both given subcutaneously thrice weekly. In addition, two different protein supplements have been compared; lyophilized human milk protein and a commercial cow's milk product. Total protein intake was 3 g/kg per day. Daily iron dose was 18-36 mg. "Healthy" preterm infants (n = 32, birth weight: 800-1400 g, gestational age < or = 31 weeks) were studied from age 3 to 8 weeks. The two protein regimens yielded no differences in body growth, reticulocyte count or Hb concentration. In both r-HuEpo dose groups increased number of reticulocytes followed start of treatment; higher levels were, however, found in the group receiving 100 IU/kg. Mean Hb concentration plateaued at 12 g/dl for infants receiving 100 IU/kg, at 11 g/dl in the 50 IU/kg group. Even though serum levels of ferritin and transferrin saturation indicated no iron deficiency, soluble transferrin receptor increased in both groups, more rapidly and to higher levels in the 100 IU/kg group. In addition, the number of infants having more than 8% hypochromic red cells increased in both groups. CONCLUSIONS: Commercial cow's milk protein added to human milk was as good as human milk protein supplementation in supporting growth and erythropoiesis. Fifty IU/kg r-HuEpo thrice weekly during AOP stimulated erythropoiesis significantly, but less so than 100 IU/kg. Even when using high oral doses of iron to preterms receiving r-HuEpo, our data suggested a certain degree of iron deficient erythropoiesis.

Recombinant human erythropoietin for the correction of cancer associated anemia with and without concomitant cytotoxic chemotherapy.

BACKGROUND: Chronic anemia is a common complication in patients with cancer, especially in those with advanced disease or who are under intensive chemotherapy. Because homologous blood transfusions involve some hazards, the safety and efficacy of recombinant human erythropoietin (r-HuEPO) in the treatment of anemic patients with cancer with and without concomitant chemotherapy were studied. METHODS: One-hundred two cancer patients with hemoglobin less than 11 g/dl, ferritin greater than 30 micrograms/l, and creatinine < 220 mumol/l were enrolled in the study, 94 were eligible for efficacy evaluation. Sixty-eight patients received chemotherapy (CT group) and 26 had no cytotoxic cancer treatment (NT group). Recombinant human erythropoietin was administered subcutaneously at a dose of 150 U/kg three times per week for 6 weeks; in nonresponders the dose was doubled for the subsequent 6 weeks. Response was defined as the achievement of a hemoglobin increase of 2g/dl. Clinical and laboratory parameters, including serum erythropoietin (EPO) levels, performance status, and quality of life, were investigated at baseline and monitored at regular intervals thereafter. RESULTS: Response was achieved by 52% and 62% of CT and NT patients, respectively. The highest response rates were observed in patients with lung cancer or with a histology of squamous cell carcinoma (both 80%). In responding patients, the symptoms of anemia subsided. They no longer needed blood transfusions after 4 weeks of therapy; and both their performance status and quality of life improved significantly. The NT patients achieved slightly more favorable results on lower weekly doses: 450 U/kg/week in NT versus 570 U/kg/week in CT patients. Serum EPO levels were higher in nonresponders at baseline and further increased during the course of treatment. Recombinant human erythropoietin was well tolerated by all patients. CONCLUSION: This multicenter study in a large patient collective shows that r-HuEPO treatment represents a safe and effective means to increase the red cell mass and eliminate the need for blood transfusions in approximately 50% of the patients with chronic anemia of cancer. Responding patients not only have increased levels of hemoglobin, but their performance status also improves significantly, and they enjoy a significantly enhanced quality of life.