Direct and indirect causes of sex differences in mercury concentrations and parasitic infections in a marine bird.

In many animal species, males and females differ in their levels of contaminants and/or parasitic infections. Most contaminants and gastro-intestinal parasites are obtained through prey ingestion, and thus the causes of sex differences in the distribution of these factors might follow similar pathways. We studied the northern common eider duck (Somateria molissima borealis) as an avian model, and used directed separation path analysis to explore the causes of sex differences in mercury (Hg) and gastro-intestinal helminths. Two trophically transmitted helminths were examined: a cestode (Lateriporus sp.) and an acanthocephalan (Polymorphus sp). We found that the number of Lateriporus sp. varied positively with stable isotope signature (as indicated by δ(15)N in eider breast muscle tissue), and negatively with crustaceans being present in the short term diet. We also found that Polymorphus sp. varied positively with eider tissue stable isotope signature. However, Polymorphus sp. varied negatively with sex indirectly through condition and liver mass. Similarly, Hg concentrations also varied negatively with sex indirectly through condition and liver mass, with both Polymorphus sp. intensity and Hg concentrations significantly higher in males. We found that model fit increased when a negative relationship between the two helminth species was included, suggesting a yet unknown causal mechanism linking these parasites. Our findings suggest that although Hg and gastro-intestinal parasites are both trophically transmitted through the eider's prey items, the factors that contribute towards bioaccumulation of these two burdens differ in source, likely caused by several different factors and may potentially influence each other.

Immunological effects of an arginine side chain contaminating synthetically prepared peptides.

The side chain, 4-methoxy-2,3,6-trimethylbenzenesulphonyl (Mtr), is a protective group coupled to arginine to mask the omega-nitrogen, in order to protect the guanidino function during peptide synthesis by the 9-fluorenylmethoxycarbonyl (Fmoc) procedure (Walker, 1994). This group is removed at the completion of peptide synthesis; however, the cleavage process can be incomplete. We have found that animals injected with a mixed population of pure, i.e. unmodified, and Mtr-containing MBP peptides have an immunodominant humoral response to the Mtr-bearing peptide. This response is dependent on the characteristics of the MBP peptide involved. For two MBP peptides, the Mtr-containing peptide had increased binding to antibody over pure peptide. For two other peptides, only the Mtr-containing peptide bound antibody while the unmodified peptide did not. In a separate system involving a polyclonal response to an unrelated peptide from beta2-microglobulin (beta2 m), the dominance of the Mtr group was also evident. These results provide further evidence that a small side chain on a single amino acid in a peptide can markedly alter the immunogenicity and antigenicity of that peptide for antibody reactivity. This evidence emphasizes the need for a critical awareness of each component of peptide synthesis and its potential to alter the immunoreactivity of the final product.

Measurement of Whole-Body CO2 Production in Birds Using Real-Time Laser-Derived Measurements of Hydrogen (δ(2)H) and Oxygen (δ(18)O) Isotope Concentrations in Water Vapor from Breath.

The doubly labeled water (DLW) method is commonly used to measure energy expenditure in free-living wildlife and humans. However, DLW studies involving animals typically require three blood samples, which can affect behavior and well-being. Moreover, measurement of H (δ(2)H) and O (δ(18)O) isotope concentrations in H2O derived from blood using conventional isotope ratio mass spectrometry is technically demanding, time-consuming, and often expensive. A novel technique that would avoid these constraints is the real-time measurement of δ(2)H and δ(18)O in the H2O vapor of exhaled breath using cavity ring-down (CRD) spectrometry, provided that δ(2)H and δ(18)O from body H2O and breath were well correlated. Here, we conducted a validation study with CRD spectrometry involving five zebra finches (Taeniopygia guttata), five brown-headed cowbirds (Molothrus ater), and five European starlings (Sturnus vulgaris), where we compared δ(2)H, δ(18)O, and rCO2 (rate of CO2 production) estimates from breath with those from blood. Isotope concentrations from blood were validated by comparing dilution-space estimates with measurements of total body water (TBW) obtained from quantitative magnetic resonance. Isotope dilution-space estimates from δ(2)H and δ(18)O values in the blood were similar to and strongly correlated with TBW measurements (R(2) = 0.99). The (2)H and (18)O (ppm) in breath and blood were also highly correlated (R(2) = 0.99 and 0.98, respectively); however, isotope concentrations in breath were always less enriched than those in blood and slightly higher than expected, given assumed fractionation values between blood and breath. Overall, rCO2 measurements from breath were strongly correlated with those from the blood (R(2) = 0.90). We suggest that this technique will find wide application in studies of animal and human energetics in the field and laboratory. We also provide suggestions for ways this technique could be further improved.

Urinary myelin basic protein-like material in patients with multiple sclerosis during interferon beta-1b treatment.

OBJECTIVES: To determine levels of urinary myelin basic protein-like material (MBPLM) in patients with multiple sclerosis (MS) openly treated with interferon beta-1b and to correlate these with clinical changes. BACKGROUND: Levels of urinary MBPLM correlate with the presence of the progressive phase of MS and with the disease burden detected on T2-weighted, cranial magnetic resonance imaging. Measurement of urinary MBPLM level may be a feasible test for monitoring or predicting response to therapeutic measures. DESIGN AND METHODS: In a prospective study at one site, 166 patients with MS (131 with relapsing-remitting [RR] and 35 with secondary progressive [SP] disease) were treated for a minimum of 1 year and up to 3 years with interferon beta-1b and underwent assessment for neurologic disability (Expanded Disability Status Scale and Scripps Neurological Rating Scale) and change in disease subtype. Urine samples were obtained at 1219 of 1378 clinic visits, and urinary MBPLM level was determined and related to creatinine level to adjust for renal function. RESULTS: Statistical analysis using the general linear models procedure confirmed previous findings that the level of urinary MBPLM related to urinary creatinine level (MBPLM/creatinine) was higher (P<.001) in patients with SP than RR MS. Of the 131 patients with RR MS, SP disease developed in 13 during the observation period. Compared with those in the RR group, the RR to SP group had a higher level (P<.001) of urinary MBPLM and did not differ from the SP group. CONCLUSIONS: The level of urinary MBPLM is higher in SP MS than RR MS but not in RR MS that converts to SP MS. Level of urinary MBPLM may permit the examination of treatment tested to prevent RR disease from becoming progressive.

Leukoencephalopathy associated with cobalamin deficiency.

Patients with cobalamin deficiency may experience cognitive impairment or neuropsychiatric symptoms. Although abnormalities of central myelin are the presumed cause of these manifestations, there is a paucity of reports of white matter lesions as shown on neuroimaging studies, and the effects of cobalamin replacement on these lesions are not known. We report a man with subacute cognitive impairment associated with cobalamin deficiency and remarkable confluent white matter abnormalities on MRI, confirmed by biopsy. With cobalamin replacement, both his cognitive deficits and imaging abnormalities partially resolved. This case indicates that leukoencephalopathy, in the absence of anemia or myelopathy, should be added to the spectrum of disorders associated with cobalamin deficiency. Early detection and treatment may be associated with a greater potential for recovery.

A cross-reactive anti-myelin basic protein idiotope in cerebrospinal fluid cells in multiple sclerosis.

We wanted to find evidence of antibody to myelin basic protein (MBP) in patients with MS by detecting their shared usage of immunoglobulin genes. As demonstrated by the idiotopes (i.d.) of murine monoclonal antibody to peptides of MBP, there is limited use of the variable (V) region immunoglobulin genes for the immune response in mice to this encephalitogenic protein. Cross-reactive Ids have been detected across different murine strains and shared by T and B cells. One cross-reactive Id, designated as 845D3 Id, is located on the V region of kappa light chains of two murine monoclonal antibodies, one to MBP peptide 80-89 and the other to MBP peptide acetyl 1-9. To examine the occurrence of 845D3 Id in MS, we used the V region of a light chain (VL) of one of the monoclonal antibodies to probe the VL genes expressed in B cells in CSF of 50 patients (31 MS and 19 non-MS). The VL genes expressed in B cells found in CSF were amplified by polymerase chain reaction using universal human V-region primers. The 845D3 Id probe detected the Id+ V region in the CSF of 14 of 31 MS patients, 1 of 9 patients with other neurologic diseases, and 1 of 10 non-neurologic patients. The gene product was more common in but not restricted to CSF with oligoclonal bands. The presence in CSF of MS patients of a cross-reactive Id to different MBP peptides is indicative of an immune response to this encephalitogenic myelin protein in a segment of MS patients. These findings are also evidence for limited usage of V-region Ig genes in the immune response of humans to MBP and the possible importance of an Id network for MBP in demyelinating disease.

Perforation of the ileum as a complication of suprapubic catheterization.

Although suprapubic catheterization is a useful technique in managing the postoperative patient who requires prolonged urinary drainage, the potential exists for iatrogenic damage to the abdominal contents. Two cases of perforation of the distal ileum occurring during catheter placement after vaginal procedures are presented. Such complications may be kept at a minimum by adequate bladder distention, careful bladder palpation, placement of the patient in the Trendelenburg position before filling the bladder, and catheter insertion before closure of the surgical incision.

Surgery for congenital absence of the vagina.

The Counsellor modification of McIndoe's procedure was used to create a vagina in 12 of 15 patients who presented with Rokitansky-Kuster-Hauser syndrome. Eighty percent of these patients, followed postoperatively from 4 months to 8 years, report satisfactory coital function. Our experience suggests that a malleable stent fashioned to conform to the surgically created neovagina is superior to a preformed, nonmoldable stent to which the endopelvic fascial dissection must conform.

Diagnostic and therapeutic modalities in women with galactorrhea.

Prolactin response to various pharmacologic agents was tested and hypocycloidal polytomograms of pituitary sellae were performed in 77 women with galactorrhea. Polytomographic findings of pituitary sellae and the results of hypothalamic-pituitary tests were analyzed retrospectively in 18 patients with pituitary adenoma. Of the patients with pituitary tumor, 94% had abnormal polytomograms of sellae turcica, 89% had serum prolactin levels greater than 160 ng/ml (range, 170 to 264 ng/ml), and 78% showed abnormal response to thyrotropin-releasing hormone (TRH) stimulation test. Transsphenoidal excision of the tumor was complete in all 14 patients with microadenoma (10 mm or less in diameter) but was incomplete in 4 patients with macroadenoma and evidence of extrasellar extension. Galactorrhea ceased and normal ovulatory menses resumed after surgery in all patients with microadenoma. Twenty-five patients received bromocriptine. Twenty-three of them had hyperprolactinemia and 21 had normal sellar polytomograms. Galactorrhea ceased and normal menses occurred in 18; 6 patients conceived. Two patients with abnormal polytomography and euprolactinemia responded to bromocriptine treatment and 1 of them conceived. The findings suggest that serial prolactin levels and hypocycloidal polytomography of sella turcica are helpful in diagnosis of pituitary prolactinomas. The TRH stimulation test is also useful in evaluating these patients. Because the natural course of the prolactinomas and the long-term results of the surgical and pharmacologic treatments are unknown, ideal management has yet to be established.

Congenital release thrombocytopathy: pathophysiology and management.

Congenital release thrombocytopathy must be included in the differential diagnosis of bleeding diatheses in women. A review of the coagulation profiles of 7 patients with congenital release thrombocytopathy suggests that more sophisticated platelet aggregation studies must be performed when routine screening procedures fail to determine the cause of a clinically suspected bleeding disorder. Establishing the diagnosis helps to avoid the use of medications which cause an acquired platelet dysfunction, and contributes to adequate prophylaxis against surgical and obstetric hemorrhage.

Amenorrhea: a review of forty cases.

A retrospective analysis of the clinical data from 40 patients with amenorrhea has enabled us to reach useful generalizations applicable to the management of this problem. Chromosome studies when puberty is delayed and a thorough pelvic examination when menarche fails to appear at the proper time relative to the sequence of other pubertal events will lead to an early definitive diagnosis in most cases of primary amenorrhea. A schema for the functional categorization of patients with secondary amenorrhea is presented to obviate the necessity of obtaining a needlessly expensive battery of laboratory tests which often yield misleading or uninterpretable data.

Mixed gonadal dysgenesis without virilization.

A 19-year-old phenotypic female with primary amenorrhea and 45X,0/46X,Y chromosomal mosaicism was found to have asymmetrical gonadal dysgenesis. Her lack of virilization precludes her precise categorization in the current nomenclature of gonadal dysgenesis and she is considered a unique variant of the syndrome of mixed gonadal dysgenesis.

Removal of a presacral tumor via a Schuchardt incision.

Presacral tumors have been traditionally approached either abdominally or via a transsacral incision. We describe a perineal approach to these tumors. A patient with a presacral benign cystic teratoma is described. The tumor was removed through a Schuchardt incision with no difficulties or complications. The vaginal approach should be considered for the removal of selected presacral tumors.

Chylous metrorrhea.

Chylous is an extremely unusual cause of leukorrhea. The diagnosis is established by verification of the chylous nature of the discharge, documentation of its uterine origin, and lymphangiographic demonstration of dilated pelvic lymphatics with uterine reflux. Surgical excision of the incompetent lymphatic channels is the treatment of choice.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina.

Complete duplication of the uterus and cervix with a unilaterally imperforate vagina must be suspected when a unilateral pelvic mass terminates in a purpuric bulge of the lateral vaginal wall in a young woman with severely progressive dysmenorrhea. Intravenous pyelography will reveal renal agenesis ipsilateral to the imperforate vagina. The prompt and accurate diagnosis of this unusual anomaly should lead to transvaginal drainage of the retained menstrual fluids prior to irreversible damage of the pelvic viscera from chronic cryptomenorrhea.

Quantitative transcervical uterine cultures with a new device.

This study was initiated to examine the ability of a new device to take transcervical cultures of the endometrial cavity in the normal and postpartum uterus. Quantitative bacteriologic assessments were made. The results show there is a millionfold increase in the mean concentration of bacteria cultured from the infected puerperal uterus when contrasted with cultures from nonpregnant women and those who have just undergone repeat cesarean section. The authors conclude that the new device obtains cultures transcervically with marked reduction in contamination; however, some method for quantification of bacterial populations must complement the culture so that results differentiate between colonization and infection.

Partial vaginal agenesis with a urinary-vaginal fistula.

A patient with partial vaginal agenesis and a urinary-vaginal fistula is presented together with a review of the 12 cases reported previously. This unusual anomaly presents with cyclically recurrent hematuria; hypothetically, it results from failure of formation or canalization of the primitive vaginal plate together with partial persistence of the urogenital sinus. Surgical correction, ideally performed after puberty, requires resection of the fistula and mobilization of the apical vaginal segment for its anastomosis to the inferior vaginal pouch.

Response to mitogen during pregnancy and the postpartum period.

The influence of pregnancy, pregnancy plasma, and pregnancy-associated lhormones on the response of peripheral blood lymphocytes to two phytomitogens (PHS and PWM) was examined in a group of 17 healthy women during pregnancy and the postpartum period. No consistent disparity between pregnancy, postpartum, and control tests was noted in either intrinsic lymphocyte responsiveness or in the effect of autologous plasma or four pregnancy-associated hormones (estriol, progesterone, hPL, and estradiol-17 beta) on lymphocyte responsiveness.

Correlation between amniotic fluid optical density and L/S ratio.

A test that circumvents the complex methodology needed for the determination of L/S ratios has been developed. It has been observed that the optical density, measured at 400 nm, of supernatants collected from fresh amniotic fluids centrifuged at 2000 g for 10 minutes correlates with L/S ratios.

Amniotic fluid optical density and neonatal respiratory outcome.

A simple, rapid, economical, and accurate test to assess fetal pulmonary maturity on a 24-hour basis, 7 days a week, is urgently needed. A 15-minute test has been developed that correlates well with fetal pulmonary maturity. Optical density (OD) readings at 650 nm of greater than or equal to 0.15 in pigment-free, centrifuged (2000 Xg, 10 minutes) amniotic fluids obtained from gestations of 33 to 42 weeks correlate with fetal pulmonary maturity (131 of 131, 100%). When OD readings are less than 0.15 in fluids from gestations of 24 to 40 weeks, and antepartum steroids are utilized, the incidence of respiratory distress syndrome (RDS) is 8.3% (14 of 169). The true false-negative rate in this group is therefore unknown.