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.

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.

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.

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.

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.

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.

Relative drug safety and efficacy: any help for the practitioner?

Approaches are discussed for assuring that the most useful entity is prescribed when a drug is the treatment of choice. Several attributes of pharmaceutical preparations that are likely to influence health status are mentioned. Three models for increasing drug-of-choice prescribing are discussed: the regulatory model, the formulary model, and the drug use review model. Four options regarding formulary preparation are presented: the federal government, a consortium of professional groups, regional expert committees, or local groups. Research is needed to determine which methods hold promise for increasing the frequency of rational prescribing.

Pharmacokinetics in drug therapy III: Clindamycin dosage regimens for treatment of chronic osteomyelitis.

A patient case which illustrates the application of pharmacokinetic principles to the dosing of clindamycin is presented. Based on calculations of a pharmacist, a patient wtih chronic osteomylitis was successfully treated at home with oral clindamycin 300 mg every four hours. The calculations showed that adequate blood and bone levels of the drug would be reached.

Hospital formularies: organizational aspects and supplementary components.

The organizational aspects and supplementary components of 44 formularies in teaching hospitals of 500 beds or more were compared. The aspects of formularies studied included prescribing regulations and technical aids, economic considerations, information on pharmacy services and procedures, information regarding drug products, hospital regulations, and format and readability. Many inconsistencies were found in the organization of the formularies and in the types of supplementary sections they included. It is suggested that the formulary has not been employed effectively as a document for transmitting drug information and hospital regulations.

National audit of drug information centers.

A comprehensive audit of drug information centers (DICs) was conducted to obtain information on sources of funding, staffing, information resources, computerization, workload, and scope of services and activities and to examine the role of DICs in education, patient care, and research. Responses were obtained from 98 of the 121 DICs surveyed. The scope of activities and services varied considerably between centers and depended on such factors as source of funding, size of institution, academic affiliation, staffing, and workload. Many DICs are involved in writing newsletters, preparing information for pharmacy and therapeutics committee meetings, developing and updating formularies, and providing contract services to other organizations. The patient-care activities of DICs include providing consultations, performing drug-use reviews, monitoring adverse drug reactions, and coordinating investigational drug studies; DICs are also involved in training undergraduate and graduate pharmacy students and residents and conducting research projects. Large workloads and lack of time were cited most often as factors limiting DIC participation in patient-care, educational, and research activities. Because DICs are involved in a wide variety of educational, research, and patient-care activities, more emphasis should be placed on documenting the costs of these services in relation to their benefits to the institution.

Serum netilmicin levels in premature AGA infants.

Safe use of aminoglycosides requires close monitoring of serum concentrations. Limited information coupled with marked changes in fluid compartments and renal function during the first week of life in premature neonates makes interpretation of peak and trough levels very difficult. This study was designed to measure serum netilmicin levels following a 2.5 mg/kg IV push infusion. Blood samples were taken on the 5th day of therapy 1 hour before and 1, 6, and 11 hours after a dose. Fifteen premature infants weighing 1000-1500 gm at birth and 20 others whose weight ranged from 1501-2750 gm comprised the study population. All premature infants were appropriate for gestational age (AGA) and of them, only two were severely asphyxiated. At the time of the study, 10 neonates were still on respirators. Serum and urine sodium and creatinine, BUN, and urinalysis were obtained in 28 of these infants. No evidence of renal dysfunction was found. All infants received 100 mg/kg IV ampicillin every 12 hours, but none were being treated with diuretics. Serum netilmicin levels were measured by an enzymatic immunoassay, peak and trough were calculated by extrapolating the first order decay curve. Peak levels ranged from 3.4 to 14 micrograms/ml (means 6.1 +/- 2.5 micrograms/ml SD) and 90% of them were above 4 micrograms/ml. Half of the small premature infants (1000-1500 gm birthweight) presented trough values above 3 micrograms/ml. Pharmacokinetic analysis of our data predicts that a 2.5 mg/kg loading dose followed by 2 mg/kg given every 12 hours will decrease by one-half the number of small prematures exceeding the considered "safe" trough level (greater than 3 micrograms/ml).