Surgery

The purpose of this study was to evaluate the safety and pharmacokinetics of nemifitide, a synthetic antidepressant pentapeptide, following its subcutaneous (s.c.) administration by standard needle injection or by a needle-free (Biojecttrade mark) injection and to compare these two routes of administration for systemic exposure. This small-scale, randomized, single-dose, parallel design, open-label pilot study consisted of three treatment groups of four subjects each dosed as follows: group 1: 40 mg of nemifitide administered by standard needle/syringe and groups 2 and 3: 40 and 80 mg nemifitide, respectively, administered by using a needle-free (Bioject injection delivery system. Plasma concentrations of nemifitide were determined by LC/MS/MS in blood samples collected at 10 min and 0.5, 1, 2, 4, 6 and 24 h after dosing. PK parameters, including observed C(max), T(max) and AUC(0-24), were calculated and statistical analysis of the data was conducted. Safety assessments (dosing site evaluations) were done at 0.5, 1, 5 and 24 h after dosing. Vital signs and clinical laboratory tests were taken on day 1 prior to dosing and at 24 h post-dose. Adverse experiences in all subjects were observed only as drug-related local reactions at the injection sites. All were considered mild in severity and transient (resolved by 24 h after dosing). T(max) was observed at 10 min after dose and was the same in all subjects. In the three dosing groups, 1 (40 mg), 2 (40 mg) and 3 (80 mg), observed C(max) values were 226, 245 and 440 ng/ml, respectively, and AUC(0-24) values were 108, 106 and 205 ng.h/ml, respectively. Ratios of AUC(0-24) and observed C(max) for nemifitide in plasma between groups 1 and 2 were within the 80%-125% range, indicating that the two modes of drug administration resulted in similar systemic exposure to nemifitide. Pharmacokinetic parameters (AUC(0-24) and C(max)) indicate dose-proportionality between the doses of 40 and 80 mg.

medical co-morbidity and anal manometry did not correlate with functional outcome. Quality of life scores and patient satisfaction scores positively correlated with continence scores. There was a trend toward higher QOL and satisfaction scores with conversion to colostomy compared with a continence score 12. Conclusions: The long-term continence rates following a DGP are low with a high peri-operative and long-term morbidity. Selection of those patients who may benefit from DGP in the long-term is yet to be defined.

Clinical data were evaluated from an open-label, single-center, pilot study in patients with chronic refractory depression. The primary efficacy criterion was the change from baseline using the Montgomery-Asberg Depression Rating Scale. The secondary efficacy criteria were the 17-item Hamilton Depression Rating Scale and the Clinical Global Impression-Improvement scale. Response to treatment (40-240 mg once per day by subcutaneous injection for 10-20 doses) was defined as more than 50% improvement in the Montgomery-Asberg Depression Rating Scale from baseline or Clinical Global Impression-Improvement < or =2 and lasting for at least two sequential weeks. Patients with a sustained response at the end point in the acute main treatment phase were enrolled for up to 2 years in a maintenance phase of the study to determine duration of response and to initiate retreatments upon relapse. Of the 25 patients with chronic refractory depression, 11 patients showed a response for Montgomery-Asberg Depression Rating Scale and one responded according to the secondary criterion Hamilton Depression Rating Scale. In seven of the 11 responders to Montgomery-Asberg Depression Rating Scale the effects were sustained for the remainder of the acute phase. Two additional sustained responders identified according to secondary criteria (Hamilton Depression Rating Scale or Clinical Global Impression-Improvement) were also enrolled in the maintenance phase. All nine sustained responders were retreated, as needed, in the maintenance phase of the study, ranging from 71 to 660 days. Mean duration of response following initial treatment and between retreatments was around 2 months. Pharmacokinetic data indicated dose-proportional systemic exposure to the drug.

To the Editor.— Symptoms related to the gallbladder and the upper GI tract are difficult to evaluate. Referring physicians often find it difficult to differentiate between the diseases involving the two systems. If a patient has classic peptic ulcer symptoms and the radiologist finds gallstones and does not perform the GI series, he leaves the surgeon with an unknown. The GI series removes this unknown or "influences his diagnostic thinking." His surgical approach is modified accordingly. A negative examination can be just as efficacious as a positive examination.

A child with signs and symptoms of acute gastroenteritis developed localization of her pain to the right lower quadrant. A clinical diagnosis of appendicitis was made and an inflamed appendix was found at surgery. The postoperative period was marked by high spiking fevers and profuse nonbloody diarrhea. Cultures of the appendix and the stool revealed Salmonella typhimurium. Nontyphoidal Salmonella organisms are a rare cause of acute suppurative appendicitis. Intraoperative cultures of the appendix and peritoneal fluid as well as postoperative cultures of the diarrheal fluid were crucial in elucidating the cause of this patient's unusual course.

wound bed. As the thermoplastic cools, it becomes inflexible and maintains the shape of the graft. Once hardened, it can be trimmedwith scissors to extend 5 mm beyond the graft margins. Next, a piece of nonadherent dressing covered in ointment is applied to the graft, and the thermoplastic dressing is sutured or stapled into place (Figs 2 and 3). An absorbent dressing can be placed over the thermoplastic dressing. The thermoplastic bolster is removed in 5 to 7 days. In summary, the thermoplastic dressing increases surface adherence between a full-thickness skin graft and its recipientwoundbed.Once sutured into place, it immobilizes the graft against mechanical forces. One of its major advantages is that the moldable plastic can be shaped to fit the convex and concave surfaces of the nose and ear. In contrast to traditional gauze bolsters, the perforated thermoplastic dressing allows the patient to shower normally. A potential complication is the possibility of contact dermatitis in sensitive individuals. Expense may be another disadvantage based on the size, color, and number of dressings purchased. A package of 10 (33 3-in), ivory thermoplastic splints costs $46. In our clinic, we have not observed graft failure or any other adverse outcome related to this dressing. We have found it tobeapractical tool forsecuring full-thickness skingrafts.

A case demonstrating the successful use of Silastic shunts for immediate limb revascularization is presented. Temporary limb revascularization may reduce the rate of amputation in combined popliteal vessel injuries. A major cause of limb loss is delay between injury and revascularization, including transport time and time spent dealing with other injuries. Repair of the popliteal vein increases the chance of successful limb salvage. Temporary Silastic shunts can alleviate time loss while others problems are dealt with and allow rapid venous, as well as arterial, revascularization. The technical ease and rapidity of shunt placement converts a catastrophic vascular emergency into a manageable problem.

The realities of the developing world often make it difficult to apply the principles adhered to in Western medicine and healthcare. While some issues may be unique to lower and middle income countries, all attempts must be made to maintain confidentiality, obtain informed consent, and practice in a safe and just manner for all patients regardless of sex, race, and religion.

Regardless of the age of the patient, dopamine is a valuable agent for treating shock associated with an abdominal catastrophe. However, when the time is appropriate for withdrawal of dopamine, the aged do not react as do younger patients. Despite apparent adequate hydration, additional volume loading is required to avert renal failure, and the dosage of dopamine has to be decreased gradually until withdrawal is complete.