A bone marrow report of absent stainable iron is not diagnostic of iron deficiency.

The absence of stainable iron in a bone marrow aspirate is widely considered to be diagnostic of iron deficiency anemia (IDA). We re-evaluated this concept by studying a cohort of 108 consecutive bone marrow specimens from an unselected series of patients who were seen at a hematology clinic and in whom iron stores were reported as being absent. A review of the pathologic reports revealed 19 inadequate specimens and 15 with decreased, but not absent, iron stores. Thus, only 74 of the 108 cases had been accurately reported. In 37 of these cases, adequate clinical and laboratory data were available and allowed further analysis. In 18 patients, careful review of patient history, physical examination, results of endoscopic procedures, and follow-up information failed to suggest the presence of IDA (group A). The review process in the remaining 19 patients suggested the possibility of IDA (group B). Significant differences between groups A and B were observed in serum ferritin (P = 0.001) and red blood cell mean corpuscular volume (P = 0.004). In contrast, the two groups did not differ significantly in hemoglobin concentration, serum iron, total iron-binding capacity, transferrin saturation, or erythrocyte sedimentation rate. These observations suggest that a pathology report of absent bone marrow hemosiderin may be inaccurate in more than 30% of cases and, even when accurate, may not necessarily signify the presence of IDA. Measurement of the serum ferritin level is needed to confirm a clinical diagnosis.

Parameters of differentiation and proliferation in adult granulosa cell tumors of the ovary.

We evaluated parameters of cell differentiation and proliferation to improve prognostication of ovarian adult granulosa cell tumors. Recurrent tumors (n = 10, REC group) and nonrecurrent tumors (n = 30, NED group) were compared in terms of cellular atypia, nuclear area, p53 overexpression, ploidy, DNA index, mitosis count, S-phase fraction, and nucleolar organizer region number and area per cell. Cellular atypia was significantly more frequent in REC than NED tumors (50% versus 13%; P = .03). Mean nuclear area was significantly larger in the REC than in the NED group (44 microm2 versus 36 microm2; P = .006). Mitotic count was significantly higher in REC than NED tumors (mean of 4.8 versus 1.7; P = .004). S-phase fraction and ploidy did not predict outcome: neither did nucleolar organizer region numbers and area per cell, or p53 overexpression. Cellular atypia and mitotic count may help in determining the prognosis of adult granulosa tumors of the ovary. The histochemical parameters evaluated did not provide additional information.

Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice.

The present study compared cocaine-induced hyperlocomotion and cocaine i.v. self-administration in DBA/2J and C57BL/6J mice. In the locomotor activity experiment, these strains were tested for hyperlocomotion after i.p. cocaine injection (0-60.0 mg/kg), using a Digiscan Animal Activity Monitoring System. In the cocaine i.v. self-administration experiment, they were compared for their ability to acquire and maintain cocaine self-administration in operant chambers with levers as the manipulanda. Animals were first trained to respond for food as a reinforcer (condensed milk solution); they were then submitted to surgical i.v. insertion of an in-dwelling catheter, and required to respond for i.v. cocaine (0.25-4.0 mg/kg per injection) as a reinforcer. DBA/2J mice showed significantly higher maximal cocaine-induced hyperlocomotion, more rapid acquisition of cocaine self-administration, and significantly lower rates of cocaine self-administration. Cocaine concentration in the brains of DBA/2J and C57BL/6J mice failed to differ following i.p. injection, suggesting that distribution factors were not involved in the differential responses to cocaine. Although not conclusive, this pattern of effects may suggest that cocaine has greater reinforcing efficacy in DBA/2J mice, confirming genetic make-up as a determinant factor in cocaine taking behavior.

Chemoprophylaxis in US Naval aircrew transiting malaria endemic areas.

BACKGROUND: The role of chemoprophylaxis in aircrew transiting malaria endemic regions has been, and remains, a point of controversy. The recent emergence of multi-drug resistant parasites and pesticide-resistant mosquitoes have made malaria prevention and control even more challenging and complex. The primary purpose was to review the efficacy of chemoprophylaxis (as compared with no chemoprophylaxis) in U.S. Naval aircrew traveling to malaria endemic areas for short periods of time on a frequent, infrequent, or isolated basis. A secondary purpose was to generate chemoprophylaxis guidelines based on the outcomes of this review. METHODS: A comprehensive MEDLINE database search was performed for the interval from January 1966 to April 1997. Additional resources were obtained from references cited in relevant journal articles, monographs, textbooks, and U. S. government publications. Pertinent U. S. Navy publications were also reviewed. Selection criteria were developed and applied to the data. RESULTS: The investigation failed to identify any analytic studies that met selection criteria regarding the efficacy of chemoprophylaxis in U.S. Naval aircrew or aircrew surrogates transiting malaria endemic areas. The data were therefore used to qualitatively assess the risks/benefits of chemoprophylaxis and generate chemoprophylaxis guidelines. Based on the results of this review, the decision to prescribe chemoprophylaxis was strongly dependent on the following risk factors: a) geographic region; b) transmission risk; c) duration of nighttime exposure; and d) aircrew, aircraft, and mission profiles. CONCLUSIONS: Studies of adequate analytic design are needed to delineate the role of chemoprophylaxis in aircrew transiting malaria endemic areas and to validate the chemoprophylaxis guidelines suggested in this review.

Prognostic factors in adult granulosa cell tumor of the ovary.

BACKGROUND: The clinical course of adult granulosa cell tumor of the ovary is characterized by indolent growth tending toward late recurrence. A variety of clinical and pathologic parameters have previously been evaluated for prognostication with inconclusive results. METHODS: The clinical records and tumor sections of 70 patients with adult granulosa cell tumors of the ovary were reviewed. Patients with recurrent tumors (REC) (n = 19) were compared with patients who remained without disease (NED) (n = 51). RESULTS: Significant differences in stage and tumor size were noted between the two groups; however, after logistic regression analysis, only stage remained statistically significant. Pathologic evaluation revealed that Call-Exner bodies occurred more frequently in tumors of the NED patients. Cellular atypia and high mitotic rates were more frequent in the REC group; however, after logistic regression analysis, only atypia remained statistically significant. When early (< 10 years) and late recurring tumors (> 10 years) were compared, statistically significant differences were again noted: early recurring tumors had fewer Call-Exner bodies, higher mitotic rates, and higher degrees of atypia; late recurring tumors were similar to tumors in the NED patients. CONCLUSIONS: Tumor stage and, to a lesser extent, tumor size are the only clinical parameters of prognostic importance in adult granulosa cell tumors. Cellular atypia and, to lesser extents, mitotic rate and the absence of Call-Exner bodies are the only significant pathologic prognosticators. It is difficult to predict early recurrences and impossible to predict late recurrences using these clinical and pathologic parameters.

Hemorrhage alters plasma and cardiac enkephalins and catecholamines in anesthetized dogs.

Intrinsic cardiac enkephalins participate in circulatory regulation either through the modification of vagal control or vasomotor sympathetic control. We extracted, chromatographed, and assayed plasma and myocardial enkephalins from anesthetized dogs under control conditions and during hemorrhagic hypotension (2 h at 40 mmHg). Blood samples were collected at intervals during the experiment. Blood gases were stable, pH declined to 7.1, and heart rate rose. Plasma catecholamines increased and remained high throughout hypotension. Catecholamine and enkephalin immunoreactivities (ir) were unchanged in time controls. Plasma methionine-enkephalin (ME) and peptide F increased twofold and methionine-enkephalin-arginine-phenylalanine (MEAP) and peptide B increased 10- to 30-fold during hypotension. Plasma proenkephalin (ProEnk) and other large enkephalins were unchanged during hypotension. Myocardial norepinephrine was greater in the atria and both atrial and ventricular contents were decreased after hypotension. ProEnk and peptide B accounted for > 60% of the cardiac enkephalins, and their ventricular concentrations were three to four times atrial concentrations. Myocardial MEAP concentrations were 15-25 times the ME concentrations in the same tissue extracts. Hypotension increased myocardial peptide B and ProEnk, and ME, MEAP, and peptide F were unchanged. The data demonstrate a preferential processing to or retention of MEAP rather than ME-ir enkephalins in the heart. The data also indicate that myocardial MEAP-ir enkephalins respond to changes in the circulatory environment and appear in the plasma during hemorrhagic hypotension.

Pericardial repair depresses canine cardiac catecholamines and met-enkephalin.

Decreased cardiac catecholamines were observed following incision and repair of the pericardium in sham-operated vs. unoperated control dogs. Animals were assigned to five groups: unoperated, sham-operated intact pericardia, open pericardia, sutured pericardia and complete ventricular sympathectomy. Hearts were collected four weeks after surgery. Sympathectomy decreased catecholamine content when compared to all other groups. Hearts with open/sutured pericardia contained significantly less catecholamines than controls. When the pericardium was intact or left open following incision, cardiac catecholamines were unchanged compared to unoperated controls. Since opioid peptides are colocalized with catecholamines, we measured met-enkephalin and met-enkephalin-arg-phe, proenkephalin A peptide products, in parallel samples. Similar to norepinephrine, met-enkephalin was decreased following both sympathectomy and pericardial repair. However, met-enkephalin-arg-phe, which may be more associated with the myocardium than its innervation, was not changed by any treatment. The sutured pericardium more than the stress of surgery apparently alters the tissue catecholamines and enkephalin. This may have resulted from the mechanical friction at the site of repair. Epinephrine and met-enkephalin contents in sympathectomized hearts were significantly lower than unoperated controls but were not significantly different from the intermediate values observed in the sutured group. The functional consequences of these changes on neuroendocrine status are unclear and will require further evaluation. The results also emphasize the need for careful attention to proper controls for surgical studies.

Microbial keratitis in children.

In a five-year review, we identified 29 cases of microbial infection in 28 patients who were 16 years old or younger. Herpes simplex infections were excluded. Predisposing factors included trauma (ten cases, 34%), severe systemic illness (eight cases, 27%), contact lens use (seven cases, 24%), exposure keratopathy (seven cases, 24%), and previous ocular surgery (six cases, 21%). A total of 24 microorganisms were identified in cultures of corneal scrapings from 22 of the 29 cases; two cases involved polymicrobial infections. Of the 24 identified pathogens, gram-positive cocci were the most common (12). Other microorganisms included gram-negative bacteria (five) and fungi (four). Isolated cases of Acanthamoeba species, Borrelia burgdorferi, and Bacillus species were also present. Therapy with intensive topical antibiotics was successful in this series. The rate of surgical intervention (6/29, 21%) was similar to that of previous reports.

Early diagnosis of infectious keratitis with in vivo real time confocal microscopy.

The tandem scanning confocal microscope (TSM) was adapted for in vivo examination of the cornea in rabbits with experimental bacterial and fungal keratitis. Compared to slit lamp biomicroscopy, the TSM provides superior lateral and axial resolution and serial optical sectioning capability, which may be useful for identification of corneal pathogens in the early stages of infection. We used the TSM to examine normal rabbit eyes infected with bacteria (Bacillus cereus) and a filamentous fungus (Aspergillus). We also examined a human cornea removed by penetrating keratoplasty after a clinical diagnosis of amoebic keratitis. In the early stages of bacterial infection, slit lamp examination revealed a nonspecific minimal stromal haze and limbal injection indistinguishable from sterile ulcers and epithelial defects. With the TSM, bacteria were visible as highly refractile bodies in the epithelium and superficial stroma. Branching fungal hyphae were also easily identified by the TSM, as were Acanthamoeba cysts and parasites in the subepithelial stroma. Our results indicate that this technique may provide a new modality for quickly and accurately identifying the agent of corneal infection, thereby facilitating prompt and appropriate treatment.

Cystoid macular edema following corneal-relaxing incisions.

We believe that this is the first report of cystoid macular edema following corneal-relaxing incisions. Both cases we describe occurred in pseudophakic eyes, one of which contained an ultraviolet light-absorbing intraocular lens. One case was complicated by a corneal perforation and postoperative inflammation. The other case had no apparent intraoperative or postoperative complications other than the cystoid macular edema. In both cases, the cystoid macular edema resolved after the institution of medical treatment, and visual acuity returned to preoperative levels.

Epikeratophakia with commercially prepared tissue for the correction of aphakia in adults.

The records of all adult patients at Louisiana State University Eye Center, New Orleans, who underwent epikeratophakia for aphakia with commercially prepared tissue since February 1984 were reviewed. The epikeratophakia lenticule was maintained in 37 (92.5%) of 40 patients; complications required the removal of three tissue lenses. The average refractive error three months after surgery was +0.67 +/- 1.97 diopters; 25 (90%) of 28 patients were within 3 D of emmetropia. At six months, the average refractive error was -0.18 +/- 2.27 D. Fourteen (58%) of 24 patients whose visual acuity was 20/40 or better with spectacles before surgery achieved 20/40 spectacle visual acuity three months after surgery, as did ten (59%) of 17 patients at six months and five (83%) of six patients at 12 months. The results in these recent cases are better than in previously reported series and reaffirm the usefulness of epikeratophakia in the treatment of aphakia.

Peripheral corneal disorders.

The peripheral cornea is anatomically and physiologically distinct from its central counterpart. The major differences relate to the gradual transition of corneal tissues to those of the conjunctiva, episclera, and sclera; furthermore, the vascular structures, lymphatics, and inflammatory cells from these neighboring structures are intimately associated with the limbus and periphery of the cornea. The peripheral cornea is thereby predisposed to three main classes of disorders which do not normally involve the central cornea. First, local conditions affecting the sclera and conjunctiva may secondarily spread to involve the limbus and peripheral cornea. These include several infectious diseases, as well as hypersensitivity conditions, mass lesions, and degenerations. Second, due to the associated blood vessels and lymphatics, the peripheral cornea may be involved in a variety of systemic diseases, including vasculitides, autoimmune disorders, and abnormal metabolic conditions. Finally, there are several conditions, such as the noninflammatory peripheral degenerations, which primarily affect the peripheral cornea without associated ocular or systemic changes. In this review, we present a classification and discussion of the various disorders which may involve the peripheral cornea.

Comparison of the effects of Viscoat and Healon on postoperative intraocular pressure.

We compared the effects of Viscoat and Healon on postoperative increases in intraocular pressure in patients undergoing uncomplicated extracapsular cataract extraction with posterior chamber intraocular lens implantation in a prospective, randomized, single-masked study. Eleven eyes received Viscoat and 13 received Healon. The Viscoat or Healon was aspirated from the anterior chamber with the irrigation-aspiration tip of an automated irrigation-aspiration system at the end of the procedure. No prophylactic intraoperative or postoperative ocular hypotensive agents were used. Intraocular pressure was measured at three, six, 12, and 24 hours postoperatively. Compared with preoperative intraocular pressure, postoperative intraocular pressure was significantly increased in both the Viscoat group and the Healon group. Some postoperative intraocular pressures were as high as 50 to 60 mm Hg, despite removal of the viscoelastic substance at the end of surgery. There was no significant difference in the postoperative intraocular pressures of the Viscoat group and the Healon group.

Screening strategies for cervical cancer and cervical intraepithelial neoplasia.

Exfoliative cytology is a highly sensitive and inexpensive screening technique for cervical cancer and its precursors. The detection and eradication of the precursors have led to a significant fall in cervical cancer incidence rates and death rates in those areas in which there has been widespread and prolonged use. Recently, however, the utility and cost-effectiveness of cytology has been questioned, and it has been suggested that screening strategies be altered. A consideration of the effect of the transit times of cervical intraepithelial neoplasia on screening intervals and the impact of the changing patterns of cervix cancer epidemiology on screening strategy suggests that a significant change in screening intervals may be counterproductive.