Acute Cholecystitis Complicating Unrelated Disease: Etiological Considerations

The phenomenon of acute cholecystitis complicating an unrelated operation has been reported with increasing frequency, and may be preceded by a variety of operative procedures and a lack of previous biliary tract symptoms. Among eight such patients treated by us, seven developed acute cholecystitis postoperatively, and in one it was discovered during operation for bleeding duodenal ulcer. Two patients had undergone wide excision of the breast; two, highly selective vagotomy; one, nephrolithotomy; one, truncal vagotomy and gastroenterostomy; and one, left hemicolectomy and colostomy. In three patients, urgent cholecystectomy was performed, and four were treated conservatively with subsequent elective cholecystectomy. Histopathological studies revealed acute and chronic cholecystitis in all eight patients and cholelithiasis in four. One patient died in septic shock. Numerous contributing factors have been suggested, including hypovolemia and biliary stasis, as well as the presence of stones. It would appear that chronic cholecystitis or other biliary pathology, as found in our eight patients, is a major factor in the development of this manifestation.     

Are adult patients with Laron syndrome osteopenic? A comparison between dual-energy X-ray absorptiometry and volumetric bone densities

Severe short stature resulting from a deficiency in IGF-I is a prominent feature of Laron syndrome (LS). Although low bone mineral density (BMD) has been noted in LS patients examined by dual energy x-ray absorptiometry (DEXA), this technique does not take volume into account and may therefore underestimate the true bone density in patients with small bones. The aim of the present study was to evaluate the BMD yielded by DEXA in our LS patients using estimated volumetric values. Volumetric density was calculated with the following formulas: bone mineral apparent density (BMAD) = bone mineral content (BMC)/(area)(3/2) for the lumbar spine and BMAD = BMC/area(2) for the femoral neck. The study sample included 12 patients (mean age, 43.9 yr; mean height, 123.7 cm). Findings were compared with 10 osteopenic subjects without developmental abnormalities (mean age, 56 yr; mean height, 164.8 cm) and 10 healthy control subjects matched for sex and age to the LS patients (mean height, 165.5 cm). BMAD in the LS group was 0.201 +/- 0.02 g/cm(3) at the lumbar spine and 0.201 +/- 0.04 g/cm(3) at the femoral neck; corresponding values for the osteopenic group were 0.130 +/- 0.01 and 0.140 +/- 0.01 g/cm(3), and for the controls, 0.178 +/- 0.03 and 0.192 +/- 0.02 g/cm(3). Although areal BMD was significantly lower in the LS and osteopenic subjects compared with controls (P < 0.02) at both the lumbar spine and femoral neck, BMAD was low (P < 0.01) in the osteopenic group only. In conclusion, DEXA does not seem to be a reliable measure of osteoporosis in patients with LS.     

Actual Colonic Perforation in Virtual Colonoscopy: Report of a Case

Computed tomography colonography, also termed virtual colonoscopy, is a new imaging method to investigate the colon, which may be a potential alternative to the conventional endoscopic colonoscopy in some cases. The high safety profile of this imaging method was considered as an additional advantage of this procedure. A case of colonic perforation in computed tomography colonography is presented, highlighting a potential risk related to this procedure. It is assumed that perforation was the result of overinflation of air into an obstructed colon caused by a lesion at the rectosigmoid junction. Thus, it is suggested that in such cases, air insufflation should be gradual, thereby minimizing the risk of perforation.     

Inhibition of concanavalin A-induced acute T cell dependent hepatic damage in mice by hypothyroidism

Abstract: Aims/Background: Concanavalin A (Con A) activates T lymphocytes and causes acute T-cell-mediated hepatic injury in mice. Decreased thyroid hormonal production is associated with a variety of immunological manifestations, including inactivation of macrophages with reduced TNF production and reduced soluble IL-2 receptors in the serum. We have recently shown that hypothyroidism prevents the development of cirrhosis and also minimizes hepatic damage in rats with fulminant hepatic failure. In the present study we examined the effects of hypothyroidism on a mouse model of Con A induced T cell-mediated acute hepatitis. Methods: Hypothyroidism was induced both medically (MMI, PTU) and surgically. Eight groups of 10 mice each were studied: euthyroid controls (2 groups: water, Con A) and hypothyroid (6 groups: MMI, PTU, Surgical, MMI-Con A, PTU-Con A, Surgical-Con A). Results: Hepatic inflammation was significantly decreased in each of the Con A treated hypothyroid groups of mice. The serum transaminases, TNF-α and IL-6 levels were significantly elevated in the Con A treated group while near normal levels were found in the hypothyroid Con A treated groups (mean±SE AST: 1499±18 vs 78±10 IU/1, p<0.001; TNF: 2500±250 vs 135± 15 pg/ml. p<0.001, IL-6: 12,200±300 vs 1260±140 pg/ml, p<0.001, respectively). Conclusions: Hypothyroidism, independent of the mode of induction, can effectively inhibit the development of acute T cell-mediated liver damage in mice. These results suggest that some decrease in thyroid function might have a role in the prevention of immune mediated liver diseases.     

Imatinib mesylate therapy for relapse after allogeneic stem cell transplantation for chronic myelogenous leukemia

Twenty-eight adults with chronic myelogenous leukemia (CML) that had relapsed after allogeneic stem cell transplantation (SCT) received imatinib mesylate (400-1000 mg/d). Disease was in chronic phase in 5 patients, accelerated in 15, and blastic in 8 (7 medullary, 1 extramedullary); median time from transplantation to relapse was 9 months (range, 1-137 months). Thirteen patients had undergone salvage donor lymphocyte infusion (DLI) (median time from DLI to imatinib mesylate therapy, 4 months [range, 2-39 months]). The overall response rate was 79% (22 of 28 patients); the complete hematologic response (CHR) rate was 74% (17 of 23 patients), and the cytogenetic response rate was 58% (15 of 26 patients; complete response in 9 [35%] patients). CHR rates were 100% for chronic phase, 83% for accelerated phase, and 43% for blastic phase. The patient with extramedullary blastic disease achieved complete response. Cytogenetic response rates were 63% (12 of 19 patients) for chronic or accelerated phases (complete cytogenetic response in 8) and 43% for blastic phase (3 of 7 patients). At median follow-up of 15 months, 19 patients were alive, 9 with no evidence of disease. The 1-year estimated survival rate was 74%. Five patients had recurrence of grade 3 (3 patients) or grades 1 to 2 (2 patients) graft-versus-host disease (GVHD). Severe granulocytopenia developed in 43% of patients and thrombocytopenia in 27%; both conditions reversed with dose adjustments of imatinib mesylate. We conclude that imatinib mesylate effectively controlled CML that recurred after allogeneic SCT, but it was associated with side effects including myelosuppression and recurrence of severe GVHD.     

Effects of 6-mercaptopurine treatment on sperm production and reproductive performance: a study in male mice

OBJECTIVE: Azathioprine and 6-mercaptopurine interact in purine metabolism and DNA synthesis, thus their potential mutagenic effects have been of concern in the management of inflammatory bowel disease (IBD), especially in patients of childbearing age. Although several clinical studies have indicated their safety in both reproduction and pregnancy, in a recent large epidemiological study concerns were raised about their adverse effects in pregnant patients with IBD, and experimental or basic data on this subject are limited. The aim of this study was to investigate sperm production, sperm quality, and reproductive outcome following prolonged 6-MP administration to male mice. MATERIAL AND METHODS: Highly inbred Balb/c adult male mice were used. 6-MP at doses of 2, 5, and 8 mg/kg (n = 9 for each group) was given daily for 51 days and the treatment group was compared with controls. After 45 days of treatment, the mice were mated with females. Following 13 days of pregnancy, the products of conception were evaluated and live fetuses were examined for gross malformations. Sperm production and morphology were examined after 51 days of 6-MP administration. RESULTS: Treatment with 6-MP at all doses did not affect sperm morphology and sperm production in the testicular tubules, as compared with controls (70% normal sperm). However, pregnancy rates were inversely related to escalating doses of 6-MP: 55%, 41%, 28%, and 16% for control, 2, 5, and 8 mg/kg groups, respectively. Resorption rates (abortions) were 21% in the control group as compared with 45-50% in all the treatment groups, but the incidence of major congenital malformations was not increased. CONCLUSIONS: Long-term 6-MP treatment in male mice did not impair sperm production and sperm morphology. However, a significantly high rate of embryonic resorption indicated occult sperm damage. Thus, normal sperm analysis does not necessarily imply that sperm damage at genetic level did not occur. It is difficult to extrapolate from these results to the clinical use of 6-MP/azathioprine in IBD patients; however, further basic genetic testing for DNA damage and clinical follow-up are warranted.     

Erythropoietin has an anti-myeloma effect - a hypothesis based on a clinical observation supported by animal studies

Recombinant human erythropoietin (rHuEpo) was introduced into clinical practice more than a decade ago, and has been found to be effective in the treatment of several types of anemia, including anemia of end-stage renal failure and cancer-related anemia. No study has suggested that Epo might have an effect on the biology of the disease, nor any survival advantage to cancer patients treated with Epo for anemia has been reported. Here we report six patients with advanced multiple myeloma (MM) with very poor prognostic features, whose expected survival was <6 months. All six patients were treated with rHuEpo for their anemia, either without any chemotherapy or very mild chemotherapy for a short time. Yet, surprisingly they lived for 45-133 months totally from MM diagnosis and 38-94 months with rHuEpo (with a good quality of life). In fact, one patient, is still alive and well, more than 8 yr after chemotherapy was discontinued because of a resistant aggressive disease. The course in these six MM patients led us to hypothesize that Epo might have an antineoplastic or antimyeloma effect. We proceeded and tested that hypothesis in mouse models of myeloma (Mittelman M et al., Proc Natl Acad Sci USA 98:5181,2001). In these models we confirmed that rHuEpo induced tumor regression in about 50% of the BALB/c mice inoculated with MOPC-315 myeloma cells. We then presented evidence that the mechanism is a new immune-mediated phenomenon, via activation of CD8+ T cells. Furthermore, evidence from the literature supports the antineoplastic effect of Epo. Epo might be used as an adjunct immune treatment in various malignant diseases, in addition to the current regimens and chemotherapeutic protocols. Future trials should determine the role of Epo in myeloma and cancer treatment, besides clarifying concerns about the presence of Epo receptors on some tumor cells.     

Clinical aspects of ballistic peripheral nerve injury: shrapnel versus gunshot

Objectives

Ballistic injuries to peripheral nerves pose special challenges in terms of indications, timing and type of surgical intervention. The aim of the present work was to analyze our experience in the surgical treatment of peripheral nerve ballistic injuries with respect to the mechanism of injury (gunshot versus shrapnel), and identify common and dissimilar prognostic factors in both types of injury.

Methods

This study was conducted on 42 patients totaling 58 nerves. Twenty-two patients (32 nerves) were injured by gunshot and 20 patients (26 nerves) by shrapnel. Median postoperative follow-up was 33 months (range 12 months to 14 years).

Results

Overall postoperative outcome appears to be more favorable for gunshot-wound (GSW) patients than shrapnel-injured patients, especially in terms of neuropathic pain relief (75 % vs. 58 % respectively, p < 0.05). Presence of foreign particles in shrapnel injured patients has a negative impact on the surgical outcome in terms of rate of pain improvement (28 % compared to 67 % in patients with and without foreign particles, respectively). Nerve graft reconstruction, rather than neurolysis, seems to be the more beneficial treatment for shrapnel-induced neuropathic pain (100 % vs. 47 % in improvement rate, respectively). Early surgical intervention (median 2 months after injury) significantly relieved neuropathic pain in 83 % of shrapnel-injured patients compared to 58 % in patients operated later.

Conclusions

This study suggests that shrapnel injury is more destructive for nerve tissue than gunshot injury. Our impression is that early surgical intervention in shrapnel injuries and split nerve grafting (especially when small fragments are recognized in the nerve) significantly improve the patient’s functional activity and quality of life.