Evaluation of Tenidap (CP-66,248) on human neutrophil arachidonic acid metabolism, chemotactic potential and clinical efficacy in the treatment of rheumatoid arthritis

Ten patients with rheumatoid arthritis (RA) were evaluated in a placebo-controlled, double-blind study examining the clinical efficacy of a novel nonsteroidal anti-inflammatory agent: Tenidap (CP-66,248). RA patients receiving active drug therapy (n = 6) demonstrated clinically significant improvements in observer assessment of pain (p less than 0.025), painful joint count (p less than 0.010), and overall clinical assessment as based on a modified rheumatoid activity index, MRAI (p less than 0.025). In parallel laboratory assays, Tenidap was found to exhibit a significant in vitro dose-dependent inhibition of ionophore-stimulated neutrophil production of the 5-lipoxygenase product: [3H]leukotriene B4 (LTB4). Although more importantly, Tenidap was also found to exhibit an in vitro dose-dependent inhibition (IC50 20 microM) of the ionophore-stimulated release (deacylation) of the precursor [3H]arachidonic acid (AA) from membrane phospholipids. In further studies, Tenidap did not have any effect on fMLP-induced neutrophil chemotactic response. These results suggest that one of the possible mechanisms for the clinical effectiveness of this agent, may be through its effect at inhibiting the release of free AA from membrane phospholipids and therefore limiting its further metabolism into certain biologically-active inflammatory lipids.     

Delayed neuropathy and acute toxicity studies with pirimiphos-methyl in the hen

This paper describes studies aimed at determining the acute anticholinergic and delayed neurotoxic potential of the organophosphate insecticide pirimiphos-methyl (O-2-diethylamino-6-methylpyrimidin-4-yl O,O-dimethyl phosphorothioate) in the hen. Delayed neuropathy was assessed by biochemical measurement of neuropathy target esterase (NTE) activities in the brain and spinal cord, clinical signs of neuropathy over two 21-day periods and histological assessment of nervous tissue. Acetylcholinesterase (AChE) activity was also determined in the brain and spinal cord. Hens were given a single oral dose of 100 mg kg-1 pirimiphos-methyl, which was followed by a repeated dose after 21 days. Tri-o-cresyl phosphate (TOCP), 500 mg kg-1, was used as a positive control. All pirimiphos-methyl-treated hens received prophylactic doses of N-methylpyridinium-2-aldoxime methanesulphonate (P2S) and atropine sulphate. Hens dosed with pirimiphos-methyl had very low AChE activities (less than 20% of control) in both the brain and spinal cord, 24 and 48 h after dosing. In the TOCP-treated hens, the activities were about 90% of control. NTE activities in the brain and spinal cord of pirimiphos-methyl-treated hens were identical to those in the controls, while they were profoundly inhibited (greater than 80%) in the TOCP-treated hens. All hens dosed with pirimiphos-methyl showed the expected signs of AChE inhibition and, following recovery, usually by Day 5, no clinical signs of delayed neuropathy were seen. The TOCP-treated hens developed clinical signs of neuropathy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Milk consumption in older Americans.

OBJECTIVES: The purpose of this study was to identify individual characteristics associated with types and frequency of milk consumption in older American adults. METHODS: A national probability-based sample (response rate = 91%) completed a telephone survey. Generalized logit and cumulative logit analyses were used to identify predictors of and barriers to fluid milk consumption in 494 elderly people. RESULTS: The likelihood of drinking skim or 1% milk rather than whole milk increased with nutrition knowledge, income, trying to reduce cholesterol intake, and being female (P < .05). Frequency of milk consumption was higher with nutrition knowledge, frequency of milk consumption during adolescence, and following a diabetic diet but was lower with milk intolerance. CONCLUSIONS: The present results could be used to develop intervention strategies for improving milk consumption rates among older adults. These strategies might focus on increasing elderly people's awareness of milk intolerance and lactose-reduced milk products and their concern about cholesterol. The relationship between current and adolescent milk consumption suggests that intervention strategies should begin early in life.     

Symptomatic and Clinical Improvement in Morbidly Obese Patients with Gastroesophageal Reflux Disease Following Roux-en-Y Gastric Bypass

Background: Patients who suffer with gastroesophageal reflux Disease (GERD) endure a worsening of symptoms as their weight increases. When medical treatment of this condition in the morbidly obese patients fails, surgical intervention may be indicated. Choosing a procedure which not only helps achieve weight control but which also relieves symptoms and complications of GERD is the goal. We present a review of patients who have undergone Roux-en-Y Gastric Bypass (RYGBP) and related procedures for this disease. Methods: One hundred eighty-eight patients undergoing surgery for morbid obesity and for GERD in 1992-1996 were contacted by mail or phone. All of these patients had undergone preoperative esophagogastroduodenoscopy to grade the severity of their disease. Their preoperative symptoms were compared to those experienced postoperatively. Results: One hundred thirty patients underwent a RYGBP with modified Hill fundopexy, 22 patients underwent a distal gastrectomy with modified Hill fundopexy, 8 patients underwent distal gastrectomy alone and 28 patients underwent RYGBP alone. There have been no deaths. There were nine surgical complications, eight early and one at 2.5 years postoperation. Follow-up is 4-48 months. The average BMI dropped from 43 to 30.2 kg/m². Whereas all patients were on some form of medical therapy before surgery, only 14 reported the need for medication postoperatively. Conclusions: Surgical intervention for weight control and treatment of GERD has been highly successful in our experience both with respect to weight control and to the reduction of reflux symptoms. Depending upon endoscopic and operative findings a RYGBP with or without an antireflux procedure can provide dramatic improvement. Gastrectomy with antireflux modifications is appropriate in selected cases.     

Open extremity fracture penetrating the skull

We present a case in which an open fracture of the ulna penetrated the skull and caused a comminuted, depressed skull fracture with a large intraparenchymal hematoma containing bone fragments.     

Cost-effectiveness and pain medicine

The specialty of pain medicine, as noted by Lippe,“… justifies itself as a unique medical specialty by virtue of a distinct body of knowledge and a well-defined scope of practice. In common with other medical specialties, it is founded on an infrastructure of scientific research, education, and clinical practice [1].“ The traditional methods of education for healthcare providers, such as medical schools, nursing schools, physical therapy schools, and clinical psychology programs, do not prepare their students adequately for the delivery of evaluation and treatment services to patients experiencing pain. Also apparent, as evidenced by the dearth of medical literature, is that the traditional methods of educating pain specialists do not adequately prepare students for an effective approach to the realities of healthcare economics in their respective fields.The result of a lack of significant education in the economics of pain medicine can be financially devastating to a new practitioner who is practicing “good” medicine yet not meeting the financial obligations incipient in the operation of a multidisciplinary pain center or even a solo practice. One important concept in the study of healthcare economics is the issue of cost-effectiveness [2].     

Is schizophrenia genetically transmitted?

Clinicians and researchers alike have questioned and studied the origin of schizophrenia for decades. Since the early 1900s, a genetic hypothesis has been suggested. This article reviews studies on a possible genetic cause of schizophrenia by use of various methods of comparison: twins, adoption, family history, family studies, and studies of biologic markers. Most researchers conclude that schizophrenia is likely caused by a genetic predisposition coupled with environmental influences.