Shelf-lives and factors affecting the stability of morphine sulphate and meperidine (pethidine) hydrochloride in plastic syringes for use in patient-controlled analgesic devices

Published reports regarding the stability of morphine are at variance, especially in syringes used in patient-controlled analgesia (PCA) devices. In addition to the effects of container type and vehicle, reasons for this variation include the effect of excipients temperature and light during storage. Furthermore, the literature varies regarding the mechanisms of decomposition for morphine. To our knowledge, the stability of meperidine (pethidine) stored in plastic syringes has not been reported. The purposes of this study were to investigate the stability of morphine sulphate (1 and 5 mg/ml) and meperidine hydrochloride (5 and 10 mg/ml) in plastic syringes for use in PCA devices for a duration of 12 weeks, and evaluate the influence of light (240 foot-candies), temperature (-20, 4 and 23d?C), diluent (5% dextrose or normal saline), and drug concentration on the stability of these narcotic analgesics. Samples were taken bi-weekly for solutions protected from light and weekly for solutions exposed to light. Morphine sulphate and meperidine hydrochloride concentrations were quantified using independent, stability-indicating, high performance liquid chromatographic assays. The within-day and between-day coefficients of variation for these assays were 4% over each of the concentration ranges studied. Under the conditions of this study, it is proposed that although decomposition of morphine to its main product, pseudomorphine, can be interpreted using first-order kinetics, consecutive (to form the N-oxide) and parallel mechanisms (to form apomorphine) exist. Morphine solutions were more stable in normal saline than in 5% dextrose. SheIf-life data indicate that morphine is stable for at least 6 weeks when protected from light. Exposure to light accelerates morphine decomposition two to six-fold depending on the concentration, and the shelf-life is reduced to about 1 week in some instances. Meperidine solutions in both vehicles under all conditions had shelf-lives of at least 12 weeks. No effects of light were detected and no changes in solution colour were observed. This study illustrates that patients using PCA devices must be advised about shelf-lives as well as correct storage conditions to protect solutions of these drugs from environmental factors that may alter shelf-lives. Pharmacists should also note that other formulation factors such as: antioxidants, preservations, buffers, impurities, and the source and quality of containers, may significantly alter the shelf-lives of these drugs.     

Reconstruction of distal phalanx defect with microsurgical fascia latae flaps combined with rib and skin graft]

OBJECTIVE: To evaluate the clinical application of microsurgical fascia latae flaps combined with rib and skin graft for reconstruction of the distal phalanx defect. METHODS: The phalanx wounds were sutured together like syndactyly. The autologeous rib was revised to repair the bone defect of distal phalanx. The fascia latae flap was used to cover the bone exposure with microvascular anastomoses and resurfaced by a meshed split-thickness skin graft. RESULTS: 5 cases were treated successfully. The fascia latae flaps were all survived with only skin graft necrosis at the distal end in one case. It was healed spontaneously. CONCLUSIONS: The fascia latae flap is nourished by the desending branch of the lateral circumflex femoral artery. The flaps has a good blood supply and can be easily obtained with a long vascular pedicle. The flap is ideal for the reconstruction of distal phalanx defect when combined with autologeous rib implant and skin graft.     

Skin cancers and precancerous lesions in Parkinson's disease patients.

Our objective was to evaluate the frequency of neoplastic and preneoplastic skin lesions in Parkinson's disease (PD) patients when compared with an aged-matched population. We performed a cross-sectional survey in PD patients and in an age-matched control group. Patients and controls were examined by a movement disorder specialist and a dermatologist. 150 PD patients and 146 controls were included. Thirty-five PD patients (23.3%) presented skin lesions that could be classified as neoplastic or preneoplastic vs. 20 subjects in the control group (13.7%) (OR 95%, CI 1.92 [1.05, 3.51]). However, this difference lost statistical significance when adjusted for gender (recruitment of controls was matched just for age with an over representation of males in the PD group). Twenty-nine PD patients (19%) presented actinic keratosis and basal cell carcinoma was diagnosed in 4 patients (3%). Although nonconclusive, our results are in agreement with previous studies suggesting an increased risk of skin cancer in PD patients. The frequency of actinic keratosis in PD patients and the associated risk to develop melanoma recommends its screening in future epidemiological studies.     

Immunohistochemical analyses of gastric stromal tumors in Taiwanese.

BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs), identified by the presence of CD117 (KIT), were previously classified as gastric and intestinal smooth muscle tumors prior to the availability of immunohistochemical methods. This study evaluated the percentage of GISTs previously diagnosed as gastric smooth muscle tumors in our hospital during an 11-year period. METHODS: A total of 81 surgically resected gastric smooth muscle tumor specimens from 81 patients were collected from January 1986 to December 1997. Immunohistochemical studies were performed on these tumors with antibodies of CD34, CD117, smooth muscle actin (SMA), S-100, and desmin. RESULTS: Among the 81 tumors, 74 (91.4%) were CD117-positive and were classified as GISTs. Among the 74 GISTs, CD34 was positive in 72 tumors (97.3%), SMA was positive in 12 tumors (16.2%), desmin was positive in 5 tumors (6.7%), and S-100 was positive in 4 tumors (5.4%). The 7 tumors classified as non-GISTs had the following immunohistochemical characteristics: 1 was a CD117-negative CD34-positive stromal tumor (GINST) [1/81, 1.2%]; 3 were schwannomas with strong S-100-positive characteristics (3/81, 3.7%); and 3 were smooth muscle tumors with both SMA- and desmin-positive status (3/81, 3.7%). No clear relationship between CD117 or CD34 expression and prognosis was found for these tumors. CONCLUSIONS: The majority (91.4%) of gastric tumors originally diagnosed as gastric smooth muscle tumors were GISTs, except for small groups of smooth muscle tumors and schwannomas.     

Alterations in mammalian target of rapamycin signaling pathways after traumatic brain injury.

In response to traumatic brain injury (TBI), neurons initiate neuroplastic processes through the activation of intracellular signaling pathways. However, the molecular mechanisms underlying neuroplasticity after TBI are poorly understood. To study this, we utilized the fluid-percussion brain injury (FPI) model to investigate alterations in the mammalian target of rapamycin (mTOR) signaling pathways in response to TBI. Mammalian target of rapamycin stimulates mRNA translation through phosphorylation of eukaryotic initiation factor 4E binding protein-1 (4E-BP1), p70 ribosomal S6 kinase (p70S6K), and ribosomal protein S6 (rpS6). These pathways coordinate cell growth and neuroplasticity via dendritic protein synthesis. Rats received sham surgery or moderate parasagittal FPI on the right side of the parietal cortex, followed by 15 mins, 30 mins, 4 h, 24 h, or 72 h of recovery. Using Western blot analysis, we found that mTOR, p70S6K, rpS6, and 4E-BP1 phosphorylation levels were significantly increased in the ipsilateral parietal cortex and hippocampus from 30 mins to 24 h after TBI, whereas total protein levels were unchanged. Using confocal microscopy to localize these changes, we found that rpS6 phosphorylation was increased in the parietal cortex and all subregions of the hippocampus. In accordance with these results, eIF4E, a key, rate-limiting mRNA translation factor, was also phosphorylated by mitogen-activated protein kinase-interacting kinase 1 (Mnk1) 15 mins after TBI. Together, these results suggest that changes in mRNA translation may be one mechanism that neurons use to respond to trauma and may contribute to the neuroplastic changes observed after TBI.     

Exogenous advanced glycosylation end products induce diabetes-like vascular dysfunction in normal rats: a factor in diabetic retinopathy

BACKGROUND. Diabetic retinopathy has been shown to be directly associated with the degree and duration of hyperglycemia, and advanced glycosylation end products (AGEs) have been implicated in this pathological process. The purpose of the experiments reported here was to study the effect of AGE deposition on retinal vascular damage which leads to diabetic retinopathy. METHODS. Intravenous injection of exogenous AGEs was used to treat wild-type non-diabetic Sprague-Dawley rats. One of the two retinal slides from each animal was treated using immunohistochemical staining to label retinal vascular AGE deposition, the other H&E staining for counting of capillary pericytes. The results were compared with the findings in untreated wild-type and diabetic controls and in rats treated with unmodified rat serum albumin (RSA). RESULTS. After 2 weeks of continuous treatment, AGEs were identified in the retinal vascular tissue of the AGE-RSA-injected group. The average number of retinal capillary pericytes per 10x100 microscope power field was 4.313+/-0.34 (mean +/- SD) in the AGE-RSA-injected group, compared with 5.798+/-0.481 in the control group ( P<0.01). CONCLUSION. These experiments demonstrate that AGEs, independent of other metabolic factors, can induce vascular change resembling that of diabetic retinopathy.     

Optimization and validation of an ischemic wound model

Localized tissue ischemia is a key factor in the development and poor prognosis of chronic wounds. Currently, there are no standardized animal models that provide sufficient tissue to evaluate the effect of modalities that may induce angiogenesis, and in vitro models of angiogenesis do not mimic the complexity of the ischemic wound bed. Therefore, we set out to develop a reproducible ischemic model for use in wound-healing studies. Male Sprague-Dawley rats underwent creation of dorsal bipedicle skin flaps with centrally located excisional wounds. Oxygen tension, wound-breaking strength, wound area, lactate, and wound vascular endothelial growth factor (VEGF) were compared in flaps measuring 2.5 and 2.0 x 11 cm with and without an underlying silicone sheet. We found that the center of the 2.0 cm flap with silicone remains in the critically ischemic range up to 14 days without tissue necrosis (33+/-4 vs. 49+/-6 mmHg in controls). Wound healing and breaking strength were significantly impaired and tissue lactate from the center of this flap was 2.9 times greater than tissue from either nonischemic controls and 2.5 cm flap (0.23+/-0.05 mg/dL/mg sample vs. 0.09+/-0.02 and 0.08+/-0.02, respectively). Vascular endothelial growth factor was 2 times greater than the nonischemic control. This ischemic wound model is relatively inexpensive, easy to perform, reproducible, and reliable. The excisional wounds provide sufficient tissue for biochemical and histologic analysis, and are amenable to the evaluation of topical and systemic therapies that may induce angiogenesis or improve wound healing.     

Effects ofTripterygium hypoglaucum (Lévl.) Hutch on male fertility

Tripterygium hypoglaucum (Lévl.) Hutch (TH) is a perennial used in Chinese traditional medicine for the treatment of rheumatoid arthritis and various skin disorders. One study showed that daily oral doses of TH significantly reduced the fertility of male rats without apparent toxicity. The effects of daily oral doses of TH on the fertility of men taking it for the treatment of rheumatoid arthritis were evaluated. Sperm concentration, motility and motility grade all were significantly reduced in the 13 men taking TH compared to 11 untreated controls. TH therapy did not affect testosterone, FSH, LH levels, and its antifertility effects appeared to be reversible.

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Resumen Triperygium hypoglaucum (Lévl.) Hutch (TH) es una perenne usada en la medicina tradicional china para el tratamiento de artritis reumatoidea y de varios desórdenes de la piel. Un estudio demostró que orales diarias de TH reducían significativamente la fertilidad en ratas macho, sin toxicidad aparente. Se evaluaron los efectos de dosis diarias orales de TH en la fertilidad de hombres que le tomaban para el tratamiento de la artritis reumatoidea. La concentración de espermatozoides, la motilidad y el grado de motilidad, se encontraron significativamente reducidos en los 13 hombres tomando TH comparados con 11 controles no tratados. La terapia con TH no afectó los niveles de testosterona, FSH y LH y sus efectos antifertilidad parecían ser reversibles.

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Resumé LeTriperygium hypoglaucum Hutch (TH) est communément utilisé en médecine traditionnelle chinoise pour le traitement de la polyarthrite chronique évolutive (PCE) et de divers troubles cutanés. Une étude a montré que l'administation quotidienne de doses orales de TH réduisait considérablement la fécondité de rats mâles sans provoquer de toxicité apparente. On a évalué les effets de doses quotidiennes administrées par voie orale sur la fécondité d'hommes atteints de PCE et traités au TH. La concentration, la motilité et le degré de motilité du sperme avaient significativement diminué chez 13 hommes traités au TH par comparaison avec 11 témoins non traités. Le traitement au TH n'a eu aucun effet sur les niveaux de testostérone, FSH et LH et ses effets anti-fécondants semblent être réversibles.