Perforative Peritonitis—Gastrointestinal Tract May Not Always Be the Source

Perforative peritonitis is the most common surgical emergency in general surgical practice. Gastrointestinal perforation is the etiology in the vast majority of the patients. However, occasionally, other rare causes may be encountered. One such cause of peritonitis is spontaneous perforation of non-gravid uterus. Uterine perforation is a potential complication of any intrauterine procedure and may be associated with injury to surrounding blood vessels or viscera such as the urinary bladder or intestine. Spontaneous uterine perforation is rare and less than 50 cases have been reported in the English literature. We are presenting two such cases of spontaneous perforation of the uterus in elderly postmenopausal women which presented with generalized peritonitis and were clinically indistinguishable from gastrointestinal perforation.     

Therapy‐related B‐lymphoblastic leukemia associated with Philadelphia chromosome and MLL rearrangement: Single institution experience and the review of the literature

Therapy related acute lymphoblastic leukemia (t‐ALL) of B cell origin is rare and constitutes approximately 2% of all ALL. Previously compiled data on the complete cytogenetic analysis of 48 t‐B‐ALL cases suggested that MLL rearrangement at 11q23 gene locus is the most common abnormality. Philadelphia chromosome (Ph) and a normal karyotype were reported as the second and third most common karyotypes, respectively. We investigated cytogenetic karyotypes of six t‐B‐ALL cases with a pre‐B cell immunophenotype. Ph + t‐B‐ALL was noted in four of six patients previously treated with radiation and/or chemotherapy. In addition, one case demonstrated MLL rearrangement at 11q23 locus while one case demonstrated normal cytogenetic karyotype. Five of the six t‐B‐ALL patients had persistent leukemia following initiation of chemotherapy for secondary leukemia with survival ranging from 10 to 21 months. To our knowledge, only fourteen patients with Ph + t‐B‐ALL have been described in the literature. In the current study, three of four cases with Ph + t‐B‐ALL were associated with treated breast carcinoma while one patient was treated for Hodgkin lymphoma. All four patients had undergone radiation therapy. The results may indicate a plausible association between Ph+t‐B‐ALL and prior radiation exposure.     

Melatonin prevents dexamethasone‐induced testicular oxidative stress and germ cell apoptosis in golden hamster,Mesocricetus auratus

This study investigated the protective effect of melatonin on dexamethasone (Dex), an extensively used anti‐inflammatory and immunosuppressive synthetic glucocorticoid, induced testicular oxidative stress and germ cell apoptosis in golden hamster. Hamsters were randomly divided into four groups (n = 7): group I – control; group II – melatonin treated (10 mg kg^?1 day^?1); group III – Dex treated (7 mg kg^?1 day^?1) and group IV – combination of Dex and melatonin. All the injections were administered intraperitoneally for seven consecutive days. The histopathological changes, specific biochemical markers, including antioxidative enzymes, plasma melatonin level and the markers for germ cell apoptosis were evaluated. Dex administration decreased antioxidant enzyme activities (SOD, CAT, GSH‐P_X), plasma melatonin level and melatonin receptor (MT1) expression with a concomitant increase in lipid peroxidation (TBARS) and altered testicular histopathology which might culminate into increased germ cell apoptosis as evident from increased Bax/Bcl‐2 ratio and caspase‐3 expression. However, melatonin pre‐treatment enhanced enzyme activities for SOD, CAT, GSH‐P_X with a simultaneous decrease in Bax/Bcl‐2 ratio and caspase‐3 expression. Our findings clearly suggest that melatonin improved defence against Dex‐induced testicular oxidative stress and prevented germ cell apoptosis, suggesting a novel combination therapeutic approach for management of male reproductive health.     

Clinicopathological and molecular features of myeloid sarcoma as initial presentation of therapy-related myeloid neoplasms: a single institution experience

Therapy-related myeloid neoplasms (t-MN) have a common origin in prior cytotoxic therapy and/or radiation. These neoplasms include therapy-related acute myeloid leukemia, myelodysplastic syndrome (t-MDS), and myelodysplastic/myeloproliferative neoplasms (t-MDS/MPN). Myeloid sarcoma (MS), on the other hand, is a rare disease manifesting as an extramedullary collection of immature cells of myeloid lineage. Rarer still is therapy-related MS (t-MS), which has not been adequately studied due to its rarity and its lack of recognition as a unique entity among other t-MN. Here, we report what is to our knowledge the first case series of t-MS, with the aim of investigating and establishing salient clinicopathological and molecular features of this entity.     

Representative Scale-Down Lyophilization Cycle Development Using a Seven-Vial Freeze-Dryer (MicroFD®)

We have implemented the use of a small-scale, 7-vial Micro Freeze Dryer (MicroFD^®; Millrock Technology, Inc.) that has the capability to accurately control heat transfer during lyophilization. We demonstrate the ability to fine-tune the MicroFD^® vial heat transfer coefficient (K_v) to match the K_v of vials in a LyoStar III laboratory-scale unit. When the MicroFD^® is run under conditions that match the K_v of the LyoStar III, the resulting lyophilization performance between scales results in equivalent product temperature profiles and critical quality attributes for the same drying process. The proposed workflow demonstrates how exploitation of K_v control in the MicroFD^® enables cycle development of at-scale lyophilization processes using only 7 product vials. By changing the MicroFD^® K_v, laboratory and, potentially, manufacturing cycles may be simulated using only 7 product vials for tremendous active pharmaceutical ingredient savings, as long as at-scale heat transfer coefficients are well characterized.     

Degradation of a lyophilized formulation of BMS-204352: identification of degradants and role of elastomeric closures

The purpose of this study was to identify two degradation products formed in the parenteral lyophilized formulation of BMS-204352, investigate the possible role of elastomeric closures in their formation, and develop a strategy to minimize/control their formation. The first degradant was identified as the hydroxymethyl derivative (formaldehyde adduct, BMS-215842) of the drug substance formed by the reaction of BMS-204352 with formaldehyde. Structure confirmation was based on liquid chromatography/mass spectroscopy (LC/MS), nuclear magnetic resonance (NMR), and chromatographic comparison to an authentic sample of the hydroxymethyl degradation product, BMS-215842. To confirm the hypothesis that formaldehyde originated from the rubber closure, migrated into the product, and reacted with BMS-204352 drug substance to form the hydroxymethyl degradant, lyophilized drug product was manufactured, the vials were stoppered with two different rubber closure formulations, and its stability was monitored. The formaldehyde adduct degradant was observed only in the drug product vials stoppered with one of the rubber closures that was evaluated. Although formaldehyde has not been detected historically as leachable and is not an added ingredient in the rubber formulation, information obtained from the stopper manufacturer indicated that the reinforcing agent used in the stopper formulation may be a potential source of formaldehyde. The second degradant was identified as the desfluoro hydroxy analog (BMS-188929) based on LC/MS, NMR, and chromatographic comparison to an authentic sample of the desfluoro hydroxy degradation product.     

Three-dimensional hindfoot motion in adolescents with surgically treated unilateral clubfoot

Advances in imaging and computerized analyses have enabled three-dimensional bone motion in the treated clubfoot to be measured precisely. Three-dimensional translations and rotations of the talus, calcaneus, navicular, and cuboid of surgically treated clubfeet were less in magnitude and sometimes different in direction (or without motion in a specific plane) compared with the contralateral normal feet. Surgical techniques used for clubfoot treatment do not restore normal hindfoot bone motion when examined with high-resolution magnetic resonance imaging, computer reconstruction, and image analysis techniques. These data advance the knowledge of hindfoot bone motion and establish a new and quantitative objective.     

Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy: a randomized, double-blind, placebo-controlled study

We evaluated the optimal preemptive dose of gabapentin for postoperative pain relief after single-level lumbar diskectomy and its effect on fentanyl consumption during the initial 24 hours in a randomized, double-blinded, placebo-controlled study in 100 patients with American Society of Anesthesiologists physical status I and II. Patients were divided into five groups to receive placebo or gabapentin 300, 600, 900, or 1200 mg 2 hours before surgery. After surgery, patients were transferred to the postanesthesia care unit (PACU). A blinded anesthesiologist recorded the pain scores at time points of 6, 12, 18, and 24 hours in the PACU on a Visual Analog Scale (VAS; 0-10 cm) at rest. Patients received patient-controlled analgesia (fentanyl 1.0 mug/kg on each demand with lockout interval of 10 minutes); total fentanyl consumption during initial 24 hours was recorded. Data were entered into the statistical software package SPSS 9.0 for analysis (one-way analysis of variance and Student-Newman-Keuls test). Patients who received gabapentin 300 mg had significantly lower VAS score at all time points. They consumed less fentanyl (patients who received placebo processed 1217.5 +/- 182.0 versus 987.5 +/- 129.6 mug; P < 0.05). Patients who received gabapentin 600, 900, and 1200 mg had lower VAS scores at all time points than patients who received gabapentin 300 mg (P < 0.05). Increasing the dose of gabapentin from 600 to 1200 mg did not decrease the VAS score, nor did the increasing dose of gabapentin significantly decrease fentanyl consumption (702.5, 635, and 626.5 microg). Thus, gabapentin 600 mg is the optimal dose for postoperative pain relief following lumbar diskectomy.