Reversal of pathological pain through specific spinal GABAA receptor subtypes.

Inflammatory diseases and neuropathic insults are frequently accompanied by severe and debilitating pain, which can become chronic and often unresponsive to conventional analgesic treatment. A loss of synaptic inhibition in the spinal dorsal horn is considered to contribute significantly to this pain pathology. Facilitation of spinal gamma-aminobutyric acid (GABA)ergic neurotransmission through modulation of GABA(A) receptors should be able to compensate for this loss.

Spinal prostaglandin E receptors of the EP2 subtype and the glycine receptor alpha3 subunit, which mediate central inflammatory hyperalgesia, do not contribute to pain after peripheral nerve injury or formalin injection.

Inflammation, peripheral nerve injury and chemical irritants can cause central sensitization in pain pathways. Prostaglandins produced in the CNS induce central sensitization during inflammation mainly by relieving nociceptive neurons from glycinergic inhibition. We have recently identified spinal prostaglandin E receptors of the EP2 subtype (EP2 receptors) and the glycine receptor alpha3 subunit (GlyR alpha3) as signal transduction elements involved in the generation of central inflammatory hyperalgesia.

Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene.

Heat sensitivity shows considerable functional variability in humans and laboratory animals, and is fundamental to inflammatory and possibly neuropathic pain. In the mouse, at least, much of this variability is genetic because inbred strains differ robustly in their behavioral sensitivity to noxious heat. These strain differences are shown here to reflect differential responsiveness of primary afferent thermal nociceptors to heat stimuli.

Spinal inflammatory hyperalgesia is mediated by prostaglandin E receptors of the EP2 subtype.

Blockade of prostaglandin (PG) production by COX inhibitors is the treatment of choice for inflammatory pain but is also prone to severe side effects. Identification of signaling elements downstream of COX inhibition, particularly of PG receptor subtypes responsible for pain sensitization (hyperalgesia), provides a strategy for better-tolerated analgesics. Here, we have identified PGE2 receptors of the EP2 receptor subtype as key signaling elements in spinal inflammatory hyperalgesia.

GlyR alpha3: an essential target for spinal PGE2-mediated inflammatory pain sensitization.

Prostaglandin E2 (PGE2) is a crucial mediator of inflammatory pain sensitization. Here, we demonstrate that inhibition of a specific glycine receptor subtype (GlyR alpha3) by PGE2-induced receptor phosphorylation underlies central inflammatory pain sensitization. We show that GlyR alpha3 is distinctly expressed in superficial layers of the spinal cord dorsal horn.

Cyclic alternating chemotherapy of high-grade malignant non-Hodgkin lymphomas with VIM-Bleo and CHOP.

Between 1986 and 1988, 81 patients with high grade malignant non-Hodgkin lymphoma according to the Kiel classification were treated with the VIM-Bleo/CHOP-regimen: etoposide 100 mg/m2 intravenously on days 1-3, ifosfamide 1.5 g/m2 intravenously days 1-5 with mesna for prophylaxis of cystitis, methotrexate 30 mg/m2 intravenously on days 3, bleomycin 10 mg intravenously on days 8 and 15, cyclophosphamide 750 mg/m2 day 22, doxorubicin 50 mg/m2 day 22, vincristine 1.4 mg/m2 on day 22, and prednisolone 100 mg postoperatively on days 1-5 and 22-26.

[Sequential alternating chemotherapy of highly malignant non-Hodgkin's lymphomas with VIM-Bleo and CHOP. Initial results].

54 patients with high grade malignant NHL (stage II 19, stage III 10, stage IV 25 patients, medium age 56 years) were treated in an ongoing study with the VIM-Bleo/CHOP-regimen: Etoposide 100 mg/m2 i.v. days 1-3, Ifosfamide 1.

[Successful antibiotic treatment of a pulmonary infection with Nocardia asteroides (biovariety A3)].

An open lung biopsy in a 67-year-old man revealed nocardiosis as the cause of a treatment-resistant pulmonary infection. His resistance had been weakened by a non-Hodgkin lymphoma, polychemotherapy and long-term steroid medication. The nocardiosis was cured by a 26-day high-dosage regimen of imipenem and amikacin in combination.

[The pathology and clinical features of generalized lymphangiomyomatosis (author's transl)].

Generalized lymphangiomyomatosis with diffuse pulmonary involvement was diagnosed at post-mortem of a 26-year-old woman. The disease occurs only in women, during or after their reproductive phase, with chylous effusion, especially chylothorax, dyspnoea and chronic progression. It is a multitopic condition starting with a focal lesion, which has its origin in the smooth musculature of the lymphatics and probably develops in dependence on hormonal factors.