Postoperative Pyoderma Gangrenosum (PPG) After Appendectomy: A Case Report.

Pyoderma gangrenosum (PG) is a rare, poorly understood, non-infectious, autoimmune phenomenon. It is an inflammatory neutrophilic dermatosis characterized by hyperactivity of the skin and the development of papules and pustules that rapidly progress to painful ulcerations with a violaceous and necrotic border. Approximately three to six cases of PG per million of the population occur per year and in the case of postoperative pyoderma gangrenosum (PPG), it is only one to three cases per million operated people. We are presenting a 41-year-old patient with a clinical presentation of PPG, developed in the surgical site on the sixth postoperative day (POD 6) following open appendectomy for acute appendicitis. Initial treatment was for surgical site infection (SSI) with wound opening, regular dressings, and broad-spectrum antibiotics. Due to unresponsiveness to therapy and the unexpected postoperative course with the progression of skin lesions, we suspected PPG. Corticosteroid therapy was introduced in a shock dose, once daily intravenous (IV), with superb results and stopping the spread of the process after only two days. Considering the rarity of PPG, especially when it first occurs postoperatively, we believe that the image of skin changes with superficial spreading and characteristic violaceous ulcerations can be of crucial importance for early diagnosis. A multidisciplinary approach with a mandatory examination by a dermatologist is important in order to make an early diagnosis and prevent wrong treatment, with the potential worsening of the patient's condition. Atraumatic wound care and negative pressure wound therapy are recommended. Patients at risk should perioperatively receive corticosteroids and postoperatively be closely observed for the potential development of PPG. Debridement is not recommended, and surgical treatment and further tissue trauma are undesirable and even prohibited.

Metabolism of myclobutanil and triadimefon by human and rat cytochrome P450 enzymes and liver microsomes.

Metabolism of two triazole-containing antifungal azoles was studied using expressed human and rat cytochrome P450s (CYP) and liver microsomes. Substrate depletion methods were used due to the complex array of metabolites produced from myclobutanil and triadimefon. Myclobutanil was metabolized more rapidly than triadimefon, which is consistent with metabolism of the n-butyl side-chain in the former and the t-butyl group in the latter compound. Human and rat CYP2C and CYP3A enzymes were the most active. Metabolism was similar in microsomes prepared from livers of control and low-dose rats. High-dose (115 mg kg-1 day-1 of triadimefon or 150 mg kg-1 day-1 of myclobutanil) rats showed increased liver weight, induction of total CYP, and increased metabolism of the two triazoles, though the apparent Km appeared unchanged relative to the control. These data identify CYP enzymes important for the metabolization of these two triazoles. Estimated hepatic clearances suggest that CYP induction may have limited impact in vivo.

Polycyclic 4(3h)-quinazolinones survey of biological properties (Part II).

The authors present examples of polycyclic 4(3H)-quinazolinones of natural origin. Structures and syntheses of pharmacologically active (antibacterial, antifungal, antihypertensive and cardiovascular, antiasthmatic, anti-inflamatory, CNS-depresant, secretion of gastric acid inhibitors) compounds are described.

Determination of platinum in rat dorsal root ganglion using ICP-MS.

This study evaluated the performance of inductively coupled plasma mass spectrometry for the determination of platinum (Pt) in rat dorsal root ganglion. The method detection limit was found to be 0.008 ng/mL of Pt, which corresponds to 4 pg of Pt per milligram of ganglia. The standard deviations in the tissue matrix were 5.7% or better and minimum matrix effect was observed. Compared to indium, the use of iridium or a combination of iridium and bismuth as internal standard(s) provided more accurate measurement. The Pt in the tissue digestate was stable for a minimum of 46 d at levels above 0.05 ng/mL. Flow injection analysis using undiluted digestates resulted in approximately 20% signal enhancement. Internal standard correction was necessary to obtain accurate results. The method was used in initial studies in which rats were dosed with cisplatin and has shown that Pt accumulates and persists in dorsal rat ganglion following treatment.

Anti-Pneumocystis activities of aromatic diamidoxime prodrugs.

Aromatic dicationic compounds, such as pentamidine, have potent antimicrobial activities. Clinical use of these compounds has been restricted, however, by their toxicity and limited oral activity. A novel approach, using amidoxime derivatives as prodrugs, has recently been proposed to overcome these limitations. Although results were presented for amidoxime derivatives of only one diamidine, pentamidine, the authors in the original proposal claimed that amidoxime derivatives would work as effective prodrugs for all pharmacologically active diamidines. Nine novel amidoxime derivatives were synthesized and tested in the present study for activity against Pneumocystis carinii in corticosteroid-suppressed rats. Only three of the nine compounds had significant oral anti-Pneumocystis activity. The bisbenzamidoxime derivatives of three direct pentamidine analogs had excellent oral and intravenous activities and reduced acute host toxicity. These compounds are not likely candidates for future drug development, however, because they have chronic toxic effects and the active amidine compounds have multiple sites susceptible to oxidative metabolism, which complicates their pharmacology and toxicology. Novel diamidoximes from three other structural classes, containing different groups linking the cationic moieties, lacked significant oral or intravenous anti-Pneumocystis activity, even though the corresponding diamidines were very active intravenously. Both active and inactive amidoximes were readily metabolized to the corresponding amidines by cell-free liver homogenates. Thus, the amidoxime prodrug approach may provide a strategy to exploit the potent antimicrobial and other pharmacological activities of selected, but certainly not all, aromatic diamidines.

Comparative neurotoxicity of oxaliplatin, cisplatin, and ormaplatin in a Wistar rat model.

Oxaliplatin (4 mg/kg), cisplatin (2 mg/kg with 20 mg/kg mannitol) and ormaplatin (2 mg/kg) were administered i.p. twice weekly for 4.5 weeks. Lactose injections (0.9%) were used as a control for oxaliplatin and 0.9% saline injections were used as a control for cisplatin and ormaplatin. Morphometric changes to dorsal root ganglia L4-L6 were quantitated as a measure of neurotoxicity. Drug treatment resulted in a decrease in cell and nuclear area and an increase in the percentage of cells with eccentric nucleoli for neuronal cell bodies in the DRG. Immediately following treatment the order of morphometric changes was ormaplatin > cisplatin > or = oxaliplatin. The accumulation of platinum in the DRG was measured by inductively coupled plasma mass spectrometry. The order of accumulation was cisplatin > oxaliplatin > ormaplatin. Following an 8-week recovery period the order of morphometric changes to the DRG was ormaplatin approximately equal to oxaliplatin > cisplatin. This correlated with a greater retention of platinum by the DRG for ormaplatin and oxaliplatin than for cisplatin. The results suggest that ormaplatin is uniquely neurotoxic immediately following treatment in the Wistar rat model. However, following an 8-week recovery period both ormaplatin and oxaliplatin are more neurotoxic than cisplatin and this neurotoxicity correlates with a greater retention of platinum by the DRG.

Review of oral skeletal muscle relaxants for the craniomandibular disorder (CMD) practitioner.

The presence of acute or chronic muscle pain and muscle spasm is a common finding in the treatment of craniomandibular disorders. A review of the literature on the centrally acting oral skeletal muscle relaxants is presented to assist the practitioner in treating CMD. The pharmacology, pharmacokinetics, metabolism, adverse reactions and available dosage forms of the skeletal muscle relaxants are discussed. The agents reviewed are carisoprodol, methocarbamol, chlorphenesin carbamate, metaxalone, chloroxazone, orphenadrine citrate, diazepam, and cyclobenzaprine. Their mechanisms are not well defined. Most act via selective inhibition of polysynaptic pathways in the central nervous system. Most evidence for their efficacy is based on subjective responses and there is question as to the adequacy of the clinical studies to date. Based on the data all of the relaxants (possibly excepting diazepam) are better than placebo based on subjective analyses. Although combinations with analgesics provide better symptom relief, no superiority over analgesics exists. No skeletal relaxant has been shown to be superior over any other oral relaxant. Based on recent clinical suspicions, further study of multiple pharmacologic effects of newer agents is indicated.