Acute limb ischemia due to malignant arterial embolism from a metastatic germ cell tumor

Arterial tumor embolization is a rare but serious complication of neoplastic disease. The majority of these tumors are associated with primary or secondary lung malignancies, originating from pulmonary vein metastasis or from an atrial mass. Malignant germ cell tumors primarily disseminate to the retroperitoneal lymph nodes and lung, and to the brain and liver later in the course of the disease. A germ cell tumor metastasis embolizing to the iliac-femoral arterial system has not yet been reported. We report a metastatic embolism in a patient with disseminated embryonal cell carcinoma causing acute limb ischemia, managed by surgical embolectomy. The sudden development of limb ischemia in a patient with a germ cell tumor should alert the physician to the possibility of tumor embolism. © 1995 Wiley-Liss, Inc.     

Intermediate and High-Grade Gastric Non-Hodgkin's Lymphoma: A Prospective Study of Non-Surgical Treatment with Primary Chemotherapy, with or without Radiotherapy

The role of surgery as initial treatment in gastric lymphoma remains controversial. We have prospectively evaluated a stomach conservation strategy in histologically aggressive gastric lymphoma, using primary adriamycin-containing chemotherapy, followed by involved-field radiotherapy in patients with limited disease. Twenty-six patients (median age 69 years) were entered in this study; 15 had stage I disease, 7 had stage II disease and 4 had stage IV disease. The chemotherapy combinations were CHOP (18 patients) and ProMACE/MOPP (8 patients). Radiotherapy was given to 11 patients. Of the 24 patients evaluated for response, 18 (75%) achieved endoscopically-confirmed complete response and 4 (17%) partial response. During follow-up (median 22 months), none of the complete responders developed recurrent lymphoma. Gastric resection was performed in 1/26 patients who did not respond to primary chemotherapy. There were no cases of perforation, but three patients (12%) developed acute gastro-intestinal bleeding a few days after the onset of chemotherapy, one of whom required a surgical devascularization procedure. There was no treatment-related mortality. These data further support the non-surgical approach in histologically aggressive gastric lymphoma, using primary chemotherapy with or without radiation therapy.     

Bone conduction hearing on the teeth of the lower jaw

Bone conduction stimulation of the teeth of the lower jaw initiates auditory sensations. However the lower jaw is only loosely coupled to the skull by the temporo-mandibular joint. Therefore the 'classical' bone conduction pathway involving skull vibration transmission entirely along bone to the temporal-petrous bone requires further consideration. Bone conduction hearing thresholds to stimulation at the forehead and at the teeth of the upper and lower jaw were determined in human subjects. Thresholds on the teeth were better than those on the forehead and there was no difference between the thresholds measured following stimulation of the upper and lower teeth. Experiments in guinea-pigs provided evidence that vibration of the teeth leads to transmission of the audio-frequency vibrations by means of soft tissue, through skull foramina, into the skull cavity (brain and CSF) and from there by fluid channels directly into inner ear fluids, exciting the cochlea.     

Pyridophens: binary pyridostigmine-aprophen prodrugs with differential inhibition of acetylcholinesterase, butyrylcholinesterase, and muscarinic receptors

A series of "binary prodrugs" called carbaphens,(1) carbamylated derivatives on one or both of the aromatic rings of the muscarinic receptor antagonist aprophen [(N,N-diethylamino)ethyl 2,2-diphenylpropionate], were synthesized to develop binary prophylactic agents against organophosphorus intoxication. As a group, the carbaphens retained the muscarinic receptor antagonist properties of aprophen but also preferentially inhibited butyrylcholinesterase (BChE) in contrast to acetylcholinesterase (AChE). Therefore, a new series of compounds named pyridophens were designed and synthesized to achieve binary prodrugs to preferentially inhibit AChE over BChE, while still retaining the muscarinic receptor antagonism of aprophen. The pyridophens consist of the basic pyridostigmine skeleton combined with the 2,2-diphenylpropionate portion of aprophen by replacement of the diethylamino group. Three compounds, 9 (a tertiary pyridine), 10 (a quaternary pyridine), and 12 (a tertiary tetrahydropyridine), were found to be effective inhibitors of both BChE and AChE. However, 10, N-methyl-3-[[(dimethylamino)carbonyl]oxy]-2-(2'2'-diphenylpropionoxy-methyl)pyridinium iodide, inhibited AChE selectively over BChE, with a bimolecular rate constant similar to pyridostigmine. In contrast to their potent cholinesterase inhibitory activity, all of the pyridophen analogues were less potent antagonists of the muscarinic receptor than aprophen.     

Chronic inositol treatment reduces depression-like immobility of Flinders Sensitive Line rats in the forced swim test

Inositol, a precursor of the PIP cycle that was reported to have therapeutic effects in depressive patients and to be effective in two animal models of depression, was evaluated in the forced swim test using the genetic Flinders Sensitive Line (FSL) rats model of depression. Groups of rats were tested in a 2 x 2 design with Strain (FSL or Control) as one factor and Drug (Inositol or Placebo) as the second factor. Rats received chronic treatment (daily for 14 days) with inositol (1.2 g/kg) or placebo (1:2 glucose/mannitol solution). On day 14 rats were exposed to the forced swim test for 5 min and their behavior videotaped. Tapes were analyzed for three levels of activity: immobility, swimming, and vigorous struggle. Inositol countered the exaggerated immobility of FSL rats in the forced swim test, without affecting control animals. Data support our previous suggestion of inositol as a potential antidepressant.     

Melatonin production in infants

This study investigated the relationships of the excretion of the melatonin metabolite, 6-sulfatoxymelatonin, to prenatal, natal, and postnatal variables and its possible relation to psychomotor development. nocturnal urinary excretion of 6-sulfatoxymelatonin was studied over a 13-hour period in 355 term infants at 8 weeks of age (n = 320) and 16 weeks of age (n = 96). data on a variety of perinatal factors including pregnancy course, delivery, early postnatal course, birth weight, medical problems, growth (length, weight, and head circumference), and psychomotor development were collected at 1, 3, 6, 9, 12, and 18 months. the relationship between nocturnal 6-sulfatoxymelatonin excretion at 8 and 16 weeks of age and these factors was investigated and analyzed. 6-sulfatoxymelatonin levels at 16 weeks of age were significantly lower in infants with abnormal vs normal development at 3 months of age (7.27 + 1.44 vs 7.97 + 1.06, p = 0.05) as well as at 6 months of age (7.15 + 1.29 vs 7.95 + 1.10, p = 0.04). no other significant relation was evident among growth, perinatal complications, medical problems, and 6-sulfatoxymelatonin excretion at 8 weeks of age and at 16 weeks of age. low melatonin excretion in the first weeks of life correlates with delayed psychomotor achievements at 3 and 6 months of age. this association suggests a causal or predictive link between melatonin and neurodevelopment in infants.     

Chemoimmunohormonal therapy with carmustine,dacarbazine, cisplatin,tamoxifen, and interferon for metastatic melanoma: a prospective phase II study

The objective of this study was to investigate the efficacy of our treatment regimen in metastatic melanoma. Thirty patients entered the study after undergoing a thorough metastatic workup. Treatment protocol included carmustine (BCNU) (150 mg/m(2) IV, day 1) every 6 weeks, dacarbazine (DTIC) (220 mg/m(2) IV, days 1-3), and cisplatin (25 mg/m(2) IV, days 1-3) every 3 weeks, interferon A-2B (6 x 10(6) U/m daily s.c. on days 4-8 and 16-20) and tamoxifen 20 mg/day for 6 weeks. Among 29 evaluable patients, overall response was seen in 15 (52%) and complete response in 5 (17%) patients. Median duration of partial response was 4 months (range, 1-12 months); of complete response was 8 months (range, 2-14 months). Complete response continues in two patients with lung metastases. Median survival time was 8.7 months. Side effects were tolerable. Four (13%) patients developed neutropenic fever, and platelet transfusions were required in five (17%) patients. One patient died of neutropenic sepsis. Thrombocytopenia caused prolongation of the median interval between the first and second courses, and drug doses were reduced in the second course in 8 of 26 (31%) patients. Our chemoimmunohormonal regimen is efficient in metastatic malignant melanoma and can induce durable remission. Severe thrombocytopenia leads to a reduction of carmustine dose in a new protocol.