Mannose-binding lectin variant associated with severe malaria in young African children.

Mannose-binding lectin (MBL) is a serum protein which initiates innate immune responses to microbial pathogens by binding to non-self surface oligosaccharides. MBL deficiency is the most common congenital immunodeficiency of human and has been shown to predispose to infections, particularly in children and immune compromised. In a matched case-control study among 870 Ghanaian children, we examined the influence of six polymorphisms of the MBL2 gene on Plasmodium falciparum infection and severe malaria. A missense mutation resulting in low MBL activity (MBL2*C) was found in 35% of healthy controls, but in 42% of asymptomatically infected children (P=0.01), and in 46% of patients with severe malaria (P=0.007). Heterozygosity for MBL2*C was associated with increased odds of infection (odds ratio (OR), 1.6; 95% confidence interval (CI), 1.1-2.1), severe malaria (OR, 1.7; 95% CI, 1.2-2.4), and of severe anemia in particular (OR, 2.3; 95% CI, 1.4-3.8). The population attributable fraction of severe malaria cases attributable to MBL2*C heterozygosity was 17%. Our results suggest that the MBL pathway of the complement system is a critical determinant of both, susceptibility to P. falciparum infection and manifestation of severe malaria, particularly in young children in whom specific immune responses are weak or absent.

Chlamydia trachomatis and herpes simplex virus 2 infection in vulvar intraepithelial neoplasia associated with human papillomavirus.

BACKGROUND: The role of viral and bacterial co-infection is stressed in VIN. A view that VIN is a sexually transmitted disease made the area of research larger and stimulated scientists to seek other sexually transmitted factors, among which Chlamydia trachomatis and Herpes simplex are frequently examined. PURPOSE: The aim of the study was to evaluate the frequency of occurrence of HPV DNA and the frequency of co-infection with Herpes virus type 2 and Chlamydia trachomatis in VIN. MATERIAL AND METHODS: We identified archival diagnostic phase tissue specimens from 41 cases of vulvar intraepithelial neoplasia III. From the same paraffin blocks containing material from the margins of surgical sections during vulvectomy, normal epithelial tissue fragments were collected. They constituted the control group. Lesion characteristics were examined in comparison with the presence of HPV DNA, HSV-2 and Chlamydia trachomatsis. Identification was performed using PCR. RESULTS: In the study group HPV infection was found in 75.6% of cases. In 73% of cases it was HPV 16. In the control group we found HPV 16 DNA in only one case (2.43%). In the HPV positive study group HPV 16 was found in 30 (30/31) cases. In only one case (1/31) it was HPV 18 type. In the study group of 41 cases with VIN, HSV-2 infection was found in six cases (14.63%). In comparison with the control group (9.75%) the difference was not statistically significant. The frequency of occurrence of Chlamydia trachomatis in the analyzed study material was 14.63% (6/41) and in the control group it was 9.75% (4/41). The difference was not statistically significant. Statistical analyses of correlations between the occurrence of DNA HPV and HSV-2 as well as of HPV and Chlamydia trachomatis showed no correlation in either case. CONCLUSION: No correlation was found between the frequency of occurrence of HPV and HSV-2 and HPV and Chlamydia trachomatis in either group.

Phase I dose escalation study of topotecan combined with alternating schedules of paclitaxel and carboplatin in advanced solid tumors.

BACKGROUND: Combining topotecan with other cytotoxics has been problematic due to marrow suppression. A phase I trial was initiated to identify the optimal sequence and maximum-tolerated dose of topotecan in combination with paclitaxel and carboplatin. PATIENTS AND METHODS: Patients with advanced cancer and performance status ECOG < or = 2. The starting dose was paclitaxel 175 mg/m2 day 1, carboplatin AUC 6.0 day 1, and topotecan 0.5 mg/m2 daily day 1-5 (early sequence). The next course of paclitaxel and carboplatin administration was delayed to day 5 (late sequence). Treatment was repeated every three weeks. After determining maximum-tolerated dose without cytokines, granulocyte colony-stimulating factor (G-CSF) was added and further dose escalation was pursued. RESULTS: Fifty-one patients were entered; men: women ratio 30:21. Dose-limiting toxicity (DLT) for the early sequence was neutropenia at doses paclitaxel mg/m2/carboplatin AUC 5/topotecan mg/m2 (PCT) 175/5/0.75 for four to five days. DLT for the late sequence was neutropenia at PCT doses of 175/5/ 1.0 for four days. G-CSF 5 microg/kg subcutaneously starting day 6 permitted further topotecan dose escalation. After adding G-CSF, late sequence DLT was neutropenia at doses 175/5/1.25 for four days. Forty-six patients were evaluable for response and of those, there were thirteen partial responses. CONCLUSIONS: The late sequence resulted in less toxicity and was better tolerated. The early sequence maximum-tolerated dose (MTD) was 175/6/0.5 for five days. The late sequence MTD was PCT 175/5/0.75 for five days. The late sequence MTD with G-CSF was 175/5/1.0 for four days. The recommended phase II PCT dose is the late sequence 175/5/1.0 for four days with G-CSF.

Blastic variant of mantle cell lymphoma following interfollicular Hodgkin's lymphoma.

Infrequently, patients are diagnosed with Hodgkin's lymphoma and a morphologically distinct lymphoma. While specific subtypes of lymphomas (including Hodgkin's lymphoma) may present diagnostic difficulties, fine needle aspiration biopsy (FNAB) is sometimes useful in the evaluation and classification of these lymphoproliferative processes. We report a case of the blastic variant of mantle cell lymphoma following Hodgkin's lymphoma, interfollicular variant. A 66-year-old woman with a history of Hodgkin's lymphoma presented with increasing contralateral cervical adenopathy three years after receiving chemotherapy. FNAB with ancillary immunophenotypic characterization identified mantle cell lymphoma, blastic variant. Subsequent excisional biopsy confirmed this diagnosis and also aided in the exclusion of recurrent Hodgkin's lymphoma. In addition to identifying the previously unreported combination of blastic variant of mantle cell lymphoma and Hodgkin's lymphoma, this case emphasizes the utility of FNAB in evaluation of new masses in patient's with a previous diagnosis of Hodgkin's lymphoma.

Cerebral mucormycosis: proton MR spectroscopy and MR imaging.

Proton magnetic resonance spectroscopy (MRS) was integrated with magnetic resonance imaging (MRI) in the evaluation of a case of cerebral mucormycosis. MRS showed markedly elevated lactate, depleted N-acetyl aspartate and metabolite resonances attributable to succinate and acetate. The spectroscopy profile is essentially similar to that of bacterial abscess but without the commonly seen resonances of the amino acids valine, leucine and isoleucine. Our extensive literature review did not yield any reports of MRS findings on cerebral mucormycosis. MRS prospectively limited the differential diagnoses given the otherwise nonspecific and complex MR imaging findings in our immunosuppressed patient.

Angiotensin II receptor blockers in patients with ACE inhibitor-induced angioedema.

OBJECTIVE: To determine the safety of using angiotensin II receptor blockers in patients who have experienced angioedema following treatment with angiotensin-converting enzyme (ACE) inhibitors. DATA SOURCES: Clinical literature identified through MEDLINE (January 1966-August 1999). Key search terms included angioneurotic edema, angiotensin-converting enzyme inhibitors, receptors-angiotensin, and losartan. DATA SYNTHESIS: ACE inhibitor-induced angioedema occurs with an incidence of 0.1-0.5%. Alternative therapy is necessary for patients who experience this potentially life-threatening adverse effect. Since angiotensin II receptor blockers do not increase concentrations of bradykinin, the proposed mechanism of ACE inhibitor-induced angioedema, they were presumed to be safe alternatives. Recent case reports, however, document angioedema following therapy with angiotensin II receptor blockers; 32% of the reported patients experienced a prior episode of angioedema attributed to ACE inhibitor therapy. CONCLUSIONS: Until the exact cause of both ACE inhibitor- and angiotensin II receptor blocker-induced angioedema is determined, angiotensin II receptor blockers should be used with extreme caution in patients with a prior history of angioedema.

Rabdomiosarcoma de epididimo / Epididymal Rhabdomyosarcoma

Se presenta un tumor mesenquimatoso maligno originado en las estructuras paratesticulares, que corresponde a un radiomiosarcoma de epidismo. Se destaca su baja incidencia en la literatura mundial y su manejo terapeútico multidisciplinario (cirugia, radioterapia, quimioterapia). Fue intervenido en el Servicio de Urología de Antártida Hospital Privado, en el año 1993 y se presenta su evaluación y seguimiento hasta la fecha

Flow cytometric immunophenotyping of bone marrow core biopsies: report of 8 patients with previously undiagnosed hematologic malignancy and failed bone marrow aspiration.

OBJECTIVE: To report a method for flow cytometric immunophenotyping (FCI) bone marrow (BM) core biopsies in patients with hematologic malignancies of the BM who present with a failed BM aspiration ("dry tap"). DESIGN AND SETTING: Core biopsy specimens of BM were obtained from 8 patients who presented with previously undiagnosed hematologic malignancies arising in (7 cases) or secondarily involving (1 case) the BM and a dry tap. Suspensions of the BM core biopsy specimens were prepared and analyzed by FCI methods. DATA EXTRACTION AND DATA SYNTHESIS: The FCI data were analyzed in conjunction with cytomorphologic, histologic, immunohistochemical, and cytogenetic findings in all cases to determine a final diagnosis. CONCLUSIONS: The prepared BM core suspensions were viable and allowed for a complete immunophenotype profile by FCI in all cases, resulting in a clear definition of the cell of origin of the hematologic malignancy. Because of lack of preservation of architectural features and the potential for artifactual alterations of the relative frequency of abnormal cells, the FCI data must always be correlated with histologic sections of the BM biopsy.

Rabdomiosarcoma de epididimo / Epididymal Rhabdomyosarcoma

Se presenta un tumor mesenquimatoso maligno originado en las estructuras paratesticulares, que corresponde a un radiomiosarcoma de epidismo. Se destaca su baja incidencia en la literatura mundial y su manejo terapeútico multidisciplinario (cirugia, radioterapia, quimioterapia). Fue intervenido en el Servicio de Urología de Antártida Hospital Privado, en el año 1993 y se presenta su evaluación y seguimiento hasta la fecha(AU)

Use of Emla prior to circumcision.

There are insufficient data to support the use of Emla cream for circumcision in newborn infants at this time. There are no studies that adequately address safety or efficacy. Before efficacy studies can be evaluated, pharmacodynamic studies need to be completed. These studies are in progress and are closed (personal communication, Vivian Broach BSPharm, Astra Pharmaceutical Product Information Service, Astra Pharmaceutical, Westborough, MA, June 8, 1995). Subsequent studies should be performed within the first 72 hours of birth and assess the following parameters: (1) serum concentrations of metHb, lidocaine, and prilocaine and its metabolites from time zero to at least 24 hours after application of the cream; (2) application time and dose applied should be varied to assess differences in absorption, as well as onset and duration of analgesia; (3) application technique could be varied to assess the depth of analgesia, that is, application to the inner and outer surface of the prepuce versus the outer surface only. Until these studies are completed, routine use of Emla cream for local anesthesia during circumcision cannot be recommended.

Emerging indications for octreotide therapy, Part 1.

Possible new indications for the use of octreotide are discussed. In October 1988, octreotide received FDA-approved labeling for use in the management of carcinoid syndrome and vipomas. Since that time, research results and clinical experience have accumulated that suggest a potentially much broader therapeutic role for octreotide. Reports continue to be published on the use of octreotide for treating pituitary tumors, gastroenteropancreatic tumors, diabetes mellitus, AIDS-associated diarrhea, autonomic neuropathy, pancreatitis, pancreatic pseudocysts and ascites, complications of pancreatic surgery and transplantation, ileostomy-associated diarrhea, enterocutaneous fistulas, pancreatic fistulas, dumping syndrome, short bowel syndrome, and gastrointestinal bleeding. Other emerging indications for the use of octreotide include psoriasis, hypercalcemia, cancer-related pain, polycystic ovary syndrome, and certain cancers. In children, octreotide has been studied for use in treating hyperinsulinemic hypoglycemia of infancy. Along with the common adverse effects of octreotide, such as pain at the injection site and nausea, less frequent effects, such as cholelithiasis, gallbladder hypercontractility, and gastritis have now been described. Much of what has been learned is based on small uncontrolled studies and case reports, since the rarity of many of the conditions for which octreotide has shown promise has tended to preclude larger studies. As clinical experience with octreotide accumulates and better-designed trials are completed where possible, a broader therapeutic role for octreotide is likely to be recognized.

Prescription assistance programs: options for assisting the uninsured and underinsured.

The objectives of the study were to determine the prevalence of indigent patient or reimbursement assistance programs for prescription drugs sponsored by the pharmaceutical industry and to collect data describing them. A questionnaire was mailed to 121 manufacturers or marketers of prescription drugs selected from the 1990 edition of the Red Book and 1991 edition of the Physicians' Desk Reference. The availability of free drug to qualified indigent patients or the availability of experts to solve reimbursement issues was then ascertained. The general application procedures and features of both types of programs were documented. The authors found that indigent patient and reimbursement assistance programs are offered for many products by numerous pharmaceutical companies, although not always on a formal basis. Of the 69 (57%) companies responding to the survey, 46 (67%) offer indigent patient assistance programs and 31 (45%) offer reimbursement assistance programs. Application procedures and services provided vary considerably between companies. These findings suggest that the pharmaceutical industry is a potential source of assistance in procuring drugs for the indigent or underinsured patient populations and a resource for resolving insurance issues. It is essential to contact a sponsor to determine current program availability and application procedures. Further study is required to appraise the merit of such programs.

Stability of dobutamine hydrochloride in peritoneal dialysis solutions.

The stability of dobutamine hydrochloride in peritoneal dialysis solutions at 4, 26, and 37 degrees C was determined. Dobutamine (as the hydrochloride salt) was added to dialysis solutions containing 1.5% or 4.25% dextrose to concentrations of 2.5, 5.0, and 7.5 mg/mL. Samples were stored at 4, 26, and 37 degrees C to mimic refrigerator, room, and body temperature, respectively. At 0, 4, 8, and 24 hours, the samples were analyzed in triplicate by stability-indicating high-performance liquid chromatography to determine the percentage of drug remaining. More than 90% of the drug was retained under all storage conditions in 1.5% dextrose dialysate containing an initial dobutamine hydrochloride concentration of 5.0 or 7.5 micrograms/mL. The mean concentration in the samples containing an initial dobutamine hydrochloride concentration of 2.5 micrograms/mL and stored at room temperature remained greater than 90% of the initial concentration for the first four hours and then decreased to less than 90%. Dobutamine was stable in 4.25% dextrose dialysate regardless of the initial concentration or the storage condition. Dobutamine hydrochloride 5.0 and 7.5 micrograms/mL in 4.25% dextrose dialysis solution was stable under all the test conditions. Dobutamine hydrochloride 2.5 micrograms/mL was stable in 1.5% dextrose dialysate for only four hours at room temperature.

Considerations of drug therapy in patients receiving enteral nutrition.

Some basic principles to consider in giving medications to patients receiving enteral nutrition include: 1. If the patient is able to take medication by mouth, this is the preferred route. 2. Liquid medications are the preferred dosage form. 3. The use of oral medications that are not meant to be crushed for enteral tube administration should be avoided. 4. For individual doses of most medications, the tube should be flushed with at least 30 ml of water before and after administration of medications. 5. Highly concentrated solutions should be diluted with 60 ml of water. 6. When several medications are to be administered to the same patient, all medications should be delivered separately and the tube flushed with at least 5 ml of water after each dose. 7. Medications should not be added directly to the feeding formulation. 8. Drug-nutrient interactions should be considered. 9. GI side effects are the most common adverse effects that occur with enteral feedings, and treatment depends on the cause.