Effects of receptor-selective neurokinin agonists and a neurokinin antagonist on the electrical activity of spinal cord neurones in culture.

1. Rat spinal cord neurones grown in tissue culture were used to examine the electrophysiological effects of the neurokin in (NK)-selective agonists (pGlu6, Pro9) substance P(6-11) (septide; NK1, 10(-6)M) and (pGlu5, MePhe8, MeGly9)SP(1-7) (DiMe-C7; NK3, 10(-6)M). In addition, the effect of the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP (10(-5)M) on the neurokinin-evoked responses was investigated. 2. Neurokinin-evoked responses consisted of an increase in neuronal activity with or without long-lasting (mean: 50s) depolarizations of the membrane potential of up to 25mV. The latter also occurred in the presence of tetrodotoxin (10(-7)M) (direct response). 3. In a number of spinal cord neurones (n = 17) only septide induced a membrane depolarization while DiMe-C7 elicited no response. On the other hand, in 2 neurones a response was exclusively evoked by DiMe-C7. 4. The neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP had no effect of its own but blocked the septide- and DiMe-C7-induced depolarizations. It had no effect on the glutamate (10(-5)M)-evoked depolarization. 5. It is concluded that by the use of neurokinin receptor-selective agonists, subpopulations of spinal cord neurones in primary dissociated cell culture can be differentiated which express the NK1 or the NK3 receptor. Cells expressing only the NK1 receptor outnumber those expressing only the NK3 receptor subtype. Both receptors can be blocked by the neurokinin antagonist (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP.

Meningoradiculitis and encephalomyelitis due to Borrelia burgdorferi: a follow-up study of 72 patients over 27 years.

In 1987, follow-up studies were conducted on 72 patients who had had meningoradiculitis and encephalomyelitis (8 patients) due to Borrelia burgdorferi 5-27 years previously. These patients had not been treated with antibiotics, either during the acute disease or during the interval prior to follow-up studies. The patients had exhibited the typical symptoms of Bannwarth's syndrome during the acute phase. At the follow-up studies, 33 patients showed no, and 23 only mild, clinical residual symptoms including normal CSF findings and low-positive serum IgG borrelia antibody titres (IFT; ELISA). Three patients without sequelae exhibited persistent intrathecal secretion of oligoclonal B. burgdorferi-specific CSF IgG antibodies (Immunoblot; positive borrelia CSF IgG antibody titres). Thirteen patients exhibited mild-to-medium sequelae with persistent intrathecal formation of oligoclonal B. burgdorferi-specific CSF IgG antibodies, up to 21 years after the acute illness. This persistence can be interpreted as an "immunological scar syndrome". Our follow-up studies appear to indicate that neurological manifestations of B. burgdorferi infections are generally (with few exceptions) of a benign nature. Most patients can be classified as having been cured without antibiotic therapy. No late manifestations of chronic progressive CNS borreliosis comparable to that of neurosyphilis have been seen following acute untreated neuroborreliosis.

The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study.

Gentamicin incorporated in beads of polymethylmethacrylate has been shown capable of being released over a period of several months in concentrations sufficiently high to control most pathogens. The therapeutic efficacy of such beads has been demonstrated in a model of osteomyelitis of the femur in the dog. Good tolerance has been shown, both in the animal model and in tissue cultures. In forty-one patients with infection of either bone or soft tissue, mainly of the lower limb, the findings were similar. The concentrations in serum and urine were low, which excludes side-effects. The insertion of gentamicin-PMMA beads may prove to be a valuable new form of local antibiotic therapy.

[Treatment of ulcus simplex of the bladder and ulcerating radiogenic cystitis with superoxide dismutase]. / Behandlung des Ulcus simplex vesicae und der ulzerierenden radiogenen Zystitis mit Superoxiddismutase.

Treatment of ulcus simplex vesicae and post irradiation ulcer of the bladder with superoxide dismutase (SOD) is reported. Its antiinflammatory effect depends on the elimination of cytotoxic superoxide radicals from tissue. SOD is injected into the bladderwall during general anesthesia using a transurethral access. We treated 8 women, 4 of them suffering from ulcus simplex vesicae and 4 of them suffering from post irradiation ulcer of the bladder. In most cases we saw prompt relief from subjective complaints and healing of the ulceration. When necessary the injection was repeated once or twice in a fortnight. We did not see any side effects.

[Subcutaneous nodules and lung cavitated nodules]. / Nodules sous-cutanés et nodules pulmonaires excavés.

An african 22-year old man consulted because of disseminated subcutaneous nodules which appeared two months ago with an increasing number. He also complained from productive cough, wheezing and dyspnea on exertion. A chest CT-scan revealed multiple cavitated nodular lesions in both lungs.

[Iodine deficiency, congenital goiter and congenital hypothyroidism. Results of TSH screening in southern Bavaria]. / Jodmangel, kongenitale Struma und kongenitale Hypothyreose. Ergebnisse des TSH-Screening in Südbayern.

Increased TSH values (greater than or equal to 20 microU/ml) were found in 422 of 168,660 neonates born in Southern Bavaria. In 40 neonates the diagnosis of congenital hypothyroidism was confirmed (1: 4,200). The iodine excretion of healthy neonates and their mothers was on average significantly lower in the Munich than the Hamburg region. No relationship between iodine supply and congenital hypothyroidism was demonstrated. On the other hand, iodine excretion in children with neonatal goiter (17% of those with hyperthyrotropinaemia detected by screening) and their mothers was significantly lower than in control groups in the same regions. In addition, there was a significant correlation between iodine excretion of the mothers and neonates. The results confirm the need for iodine prophylaxis which should also take into account the higher needs during pregnancy. Apart from prophylactic aspects, these measures would also be in the interest of greater effectiveness and selectivity of TSH screening since it would reduce the number of cost-intensive follow-up examinations.

Induction of interferon by polyribonucleotides containing thiopyrimidines.

The influence of thioketo substitution in pyrimidine bases of double-stranded polynucleotides on interferon induction was investigated. The stabilizing effect of 2-thioketo substitution was reflected in the increased interferon inducing activity of poly(A-s2U) over that of poly(A-U). Poly(A-s2U) and poly(I)-poly(s2C) were as effective as poly(I)-Poly(C) in rabbit cells. Poly(I)-poly(C) and poly(I)-poly(s2C) were compared in several animal species. No differences in biological effects were observed in rabbits and dogs. In rodents, poly(I)-poly(s2C) was less effective and less toxic.Poly(I)-poly(s2C) was highly resistant against degradation by human serum. Further investigations seem to be justified to elucidate whether this property offers any advantages for the potential clinical utilization of poly(I)-poly(s2C).

[Experimental and pharmacokinetic studies with gentamicin PMMA beads (author's transl)]. / Experimentelle und pharmakokinetische Untersuchungen mit Gentamycin-PMMA-Kugeln.

Gentamicin PMMA beads (PMMA = polymethylmethacrylate) represent a new form of local antibiotic therapy for treating chronic bone and soft tissue infections. Gentamicin is released in high concentrations from PMMA. The therapeutic efficacy of the beads was demonstrated in a model of bone infection in dogs. Sufficiently high tissue concentrations of gentamicin were measurable for a period of 4 months. A very good tolerance of the beads was demonstrated in dogs as well as in cell cultures. High gentamicin concentrations exceeding the MBC values of relevant pathogens were measurable in patients at the site of infection. Serum and urine concentrations were low and therefore toxic side effects are excluded.

Idiopathic colonic varices: an unusual cause of massive lower gastrointestinal hemorrhage.

Varices of the entire colon are very rare. This rare cause of massive lower gastrointestinal hemorrhage is almost invariably associated with cirrhosis of the liver and consequent hypertension or portal venous obstruction. We report about a patient with massive lower gastrointestinal bleeding from extensive colonic varices. Despite extensive investigation and a follow-up of 3 years, the etiology of the colonic varices could not be determined. Only a few cases of apparent idiopathic (familial or non-familial) colonic varices have been described. Recognition of this abnormality is important, however, because colonic varices may be the cause of recurrent, frequently massive lower gastrointestinal hemorrhage. A misleading endoscopic diagnosis can lead to inappropriate biopsies, resulting in major bleeding.

Current clinical trials in Hodgkin's disease.

With the advent of modern polychemotherapy and radiation techniques, cure rates in Hodgkin's disease (HD) have improved substantially. This article summarises current concepts of treatment for early, intermediate and advanced stage HD. Current strategies focus on the balance between cure rate and toxicity. In early stages, cure rates approach 90% and new strategies mainly try to avoid toxicities. Possible approaches comprise the use of less CT or RT or leaving laparotomy. In advanced stages, polychemotherapy with 8 courses of either M(C)OPP or ABVD or M(C)OPP/ABVD is considered to be the treatment of choice, but unsatisfactory low complete remission rates, progression-free survival or freedom from treatment failure rates have to be improved. The role of additional radiotherapy after extensive chemotherapy in the treatment of advanced stages is uncertain. To achieve a better tumour control, new regimens have been developed. The Stanford group initiated the 12-week intensified hybrid protocol Stanford V. The German Hodgkin's Lymphoma Study Group (GHSG) introduced the BEACOPP protocol with time intensification and dose escalation of cyclophosphamide and etoposide. The Milan Cancer Institute tries to improve treatment outcome using high doses of single agents. One problem to be addressed in ongoing and future trials is the identification of high-risk groups allowing an early stratification of patients into more aggressive but effective regimens. Risk-adapted therapy might allow further reduction of doses in patients with early-stage Hodgkin's disease.

A prospective randomised evaluation of G-CSF or G-CSF plus oral antibiotics in chemotherapy-treated patients at high risk of developing febrile neutropenia.

BACKGROUND: Febrile neutropenia (FN) remains a major dose-limiting complication among patients treated with chemotherapy. Haematopoietic colony stimulating factors (G-CSF and GM-CSF) made possible a significant improvement in the management of FN, both in the therapeutic and in the prophylactic approach. The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia. Nevertheless, the possible role of these two interventions for secondary prevention of FN is still unclear. PATIENTS AND METHODS: We conducted a prospective randomised trial by comparing the efficacy of granulocyte-colony stimulating factor (G-CSF) and the association of G-CSF with oral antibiotics in the secondary prevention of FN. We included in our study those patients who, after an episode of FN, continued to be treated with the same chemotherapy without reduction of dose intensity. They were randomised into two groups: the first received G-CSF (group G; filgrastim, 5 microg/kg day), and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin (group G/ACC). RESULTS: Forty-eight patients were randomised (group G: n=23 and group G/ACC: n=25). There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group (p=1). With regard to the side effects, there was no significant difference in the two groups. CONCLUSION: The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity. Our study showed that the addition of antibiotics does not seem to be required.

[Iodine excretion and dietary iodine supply in newborn infants in iodine-deficient regions of West Germany]. / Jodausscheidung und alimentäre Jodversorgung bei Neugeborenen in Jodmangelgebieten der Bundesrepublik.

Urinary iodine excretion was measured on the fifth day of life in 461 neonates from nine different towns in the Federal Republic of Germany. There was a progressive fall in levels from north to south, with highest values in Hamburg (2.9 micrograms/dl) and lowest in Freiburg (1.2 micrograms/dl). All levels were lower than those of neonates in other countries in which iodine is added to salt: Stockholm (61 neonates) 9.6 micrograms/dl, Zurich (63) 4.75 micrograms/dl. Iodine analysis of mothers in G ottingen on the fifth day post-partum indicated that iodine excretion in urine of mothers with goitre (51 cases) was significantly lower than in a control group without goitre (38): 17.6 compared with 30.0 micrograms/g creatinine, and the iodine content of breast milk in the goitre group was significantly lower than that of the control group (1.75 compared with 2.5 micrograms/dl). Iodine content in artificial infant milk preparations was of a similar range. These results indicate that iodine supply during the neonatal period in the Federal Republic of Germany is very low; they support the demand for general iodine-salt prophylaxis.