Addison's disease in pregnancy: Case report, management, and review of the literature.

BACKGROUND: Addison's disease is an uncommon condition encountered during pregnancy; however, pregnant patients with Addison's disease are at higher risk for multiple pregnancy related complications. Treatment during pregnancy involves steroid replacement therapy. CASE REPORT: A 34-year-old previously healthy G2P1001 presented with lethargy, skin hyperpigmentation, polyuria, and salt craving. Laboratory evaluation showed hyperkalemia, hyponatremia, elevated ACTH, and low cortisol. The patient terminated the pregnancy due to her symptoms. She was then placed on a regimen of hydrocortisone and fludrocortisone, leading to symptom resolution. On second presentation as a G5P1031, her Addison's disease was managed with hydrocortisone and fludrocortisone. When Addison's symptoms recurred, ACTH levels were checked to determine if her current medications could be optimized. She ultimately delivered a healthy male infant vaginally. For her third presentation as a G6P2032, her pregnancy was managed in a similar manner to the previous pregnancy. CONCLUSION: There is currently minimal cohesive literature on the management of Addison's disease during pregnancy. Patients can be managed successfully by monitoring for recurrence of Addison's symptoms and adjusting medication dosing as needed.

Identification and tracking of problematic host cell proteins removed by a synthetic, highly functionalized nonwoven media in downstream bioprocessing of monoclonal antibodies.

The repertoire of complex proteins produced by the host cell during monoclonal antibody (mAb) production has generated a bottleneck in downstream bioprocessing. Low ppm levels of host cell proteins (HCPs) must be achieved at the downstream purification process stage to generate an end product suitable for use in humans. The increased demand for mAb drug products globally has driven research to focus on affordability of mAb production platforms. This has fuelled advancements in manufacturing R&D to deliver higher product titres with better economics without sacrificing product quality. This study highlights the beneficial effects of inclusion of the Emphaze™ AEX Hybrid Purifier, compared to a conventional clarification process, for removal problematic HCPs during downstream bioprocessing of mAbs. Advanced proteomic methods were used to track and identify known 'problematic' HCPs through a multi-cycle Protein A purification process. Removal of histone proteins was observed, along with an average total HCP reduction of 38-fold and an average reduction of 2.3 log in HCDNA concentration. Chromatographic clarification using the Emphaze™ AEX Hybrid Purifier in conjunction with Protein A chromatography resulted in the removal of problematic HCPs including 78 kD glucose-regulated protein, nidogen-1, heat shock proteins, actin, serine protease HTRA1 and matrix metalloproteinase-19. It is shown herein that the Emphaze™ AEX Hybrid Purifier, which is readily incorporated into a mAb purification process during the clarification stage, has the potential to increase Protein A resin lifetime and potentially reduce the number of subsequent polishing chromatographic steps needed to remove HCPs that have a tendency to co-purify with mAb products.

Random amplified polymorphic DNA analysis of Acinetobacter species isolated from worn contact lenses.

The purpose of this study was to explore the genotypes of Acinetobacter species and to compare the genotypes and phenotypes of the Acinetobacter isolated from contact lens wearers. Nineteen strains were used in the study, 13 were isolated from patients experiencing an adverse response event, and six strains were isolated from asymptomatic contact lens wearers. Random amplified polymorphic DNA and phenotypic analyses were carried out using commercially available kits. Random amplified polymorphic DNA analysis showed a higher discrimination power compared with the phenotypic analysis. The test strains were loosely clustered into six genotypic groups with no definite relation to any clinical events. These results indicate that many genotypes of Acinetobacter can cause adverse responses, and the initial source of the microorganisms rather than their clinical sequelae may determine classification.

Association of acinetobacter species with contact lens-induced adverse responses.

PURPOSE: To determine the levels of Acinetobacter species associated with normal soft contact lens wear and to determine whether Acinetobacter species are involved in adverse reactions that occur during contact lens wear. METHODS: Patients wore soft contact lenses on an extended-wear basis. The bacteria on lenses and ocular swabs during asymptomatic and symptomatic lens wear were identified using standard microbiologic methods. RESULTS: Acinetobacter species were isolated and identified from 16 (13%) of 126 patient samples. Greater numbers of Acinetobacter species were isolated from lenses of patients experiencing adverse responses than from asymptomatic patients. Acinetobacter species were isolated from patients experiencing symptomatic adverse responses in 4 (13%) of 32 cases. CONCLUSION: It appeared that Acinetobacter species colonized the eye of extended contact lens wearers at a time when the normal functioning of the eye was compromised by contact lens wear. When Acinetobacter species were in high numbers on a contact lens, an adverse response occurred. This may implicate Acinetobacter species as a contributing factor to adverse responses associated with contact lens wear.

Bacterial populations on 30-night extended wear silicone hydrogel lenses.

PURPOSE: Ocular infection and inflammation during hydrogel lens extended wear is often associated with colonization of the lenses with bacteria. This study compares colonization of a high Dk silicone hydrogel contact lens (lotrafilcon A) worn on a 30-night extended wear basis to a low Dk HEMA-based lens (etafilcon A) worn on a 6-night extended wear schedule. METHODS: The group wearing the low Dk/t soft contact lens (n = 63) replaced their lenses weekly and the group wearing high Dk/t soft contact lenses replaced their lenses monthly (n = 64). Lens allocation was assigned randomly at enrollment. Worn lenses, from one eye only, were collected aseptically and placed in sterile vials. Microbial growth on various media was enumerated and the number of colony forming units (cfu) per lens was calculated in categories of normal ocular microbiota (such as coagulase-negative staphylococci and Propionibacterium spp.) and known ocular pathogens (such as Staphylococcus aureus and gram-negative bacteria). The proportion of samples colonized with these bacteria and the extent of colonization were compared between the two groups. The proportion of sterile lenses was calculated, and the types of bacteria on each lens group were compared. RESULTS: No differences between the low and high Dk/t Soft contact lens groups were observed in the proportion of lenses colonized by Propionibacterium spp. (48% vs 43%, P = 0.4) or coagulase-negative staphylococci (47% vs 54%, P = 0.2). Similarly, no differences were found for lenses colonized by S. aureus (0% vs 2%, P = 0.1) or gram-negative bacteria (3% vs 2%, P = 0.8). The types of bacteria isolated from the high and low Dk/t lenses were similar. There were no differences in the number of sterile samples (28% vs 27%, P = 0.8) from each group. CONCLUSIONS: These findings suggest that high Dk/t silicone hydrogel materials are colonized by similar numbers and types of microorganisms during extended wear compared to HEMA-based material. Most lenses were colonized by commensal bacteria during 30-night extended wear with high Dk/t lenses and during 6-night extended wear with low Dk/t lenses. The incidence of sterile samples was the same between the high and low Dk/t soft contact lens groups.

Infiltrative keratitis associated with extended wear of hydrogel lenses and Abiotrophia defectiva.

PURPOSE: Infiltrative keratitis is a common complication associated with extended wear of hydrogel lenses. Causative bacteria are often isolated from the lens at the time of an event. We report a case where three repeated occurrences of infiltrative keratitis were associated with contamination of the contact lenses by Abiotrophia defectiva. METHODS: A 34-year-old man participating in a clinical trial of extended wear hydrogel contact lenses experienced three episodes of infiltrative keratitis. The clinical presentation was observed using a biomicroscope. At the time of each event, the contact lenses were removed aseptically and ocular swabs were taken for bacterial identification and enumeration. The condition was monitored until full resolution. RESULTS: The condition was characterized by irritation, marked bulbar and limbal injection, and multiple focal subepithelial infiltrates. Many of the infiltrates also showed overlying staining with fluorescein. In each of the three events of infiltrative keratitis, A. defectiva was cultured from the contact lens and ocular swabs. CONCLUSION: This is the first reported occurrence of infiltrative keratitis associated with A. defectiva contamination of contact lenses.

Mammographic determination of breast volume: comparing different methods.

OBJECTIVE: The purpose of this study was to compare the accuracy and reproducibility of different methods for calculating breast volume when using measurements made on mammograms. MATERIALS AND METHODS: The volumes of 32 breasts were determined by pathologic evaluation of mastectomy specimens. Two radiologists independently measured breast height and width on the preoperative craniocaudal mammograms and measured height, width, and width at half-height on mediolateral oblique mammograms. Compression thicknesses used on the craniocaudal and mediolateral oblique projections were recorded. Volume was then calculated using six different formulas. The accuracy of each method was determined and compared using bivariate and univariate linear regression analyses. Interobserver variability in measurement was also assessed. RESULTS: The most accurate method for calculating breast volume was the one that assumed a half-elliptic cylinder shape for the compressed breast in the craniocaudal projection. Measurements made on the craniocaudal view were more reproducible than those made on the mediolateral oblique view. CONCLUSION: Breast volume can be accurately and reproducibly determined on mammograms by making two measurements on the craniocaudal view and knowing the compression thickness. This information may be useful to plastic surgeons, investigators who study parenchymal patterns, and physicians who examine cancer patients being considered for breast conservation surgery.

Identification and enumeration of staphylococci from the eye during soft contact lens wear.

PURPOSE: An extensive study was conducted to identify and enumerate staphylococcal microbiota found on ocular sites during asymptomatic soft contact lens (SCL) wear. METHODS: A biochemical identification system separately grouped the eight clinically relevant staphylococci. Total counts and isolation frequencies from SCLs and ocular sites were evaluated. RESULTS: The epidermidis group was the most numerous isolate from extended wear (EW) lenses; the capitis/warneri group was the most numerous (p < 0.05) from daily wear (DW) lenses. In both DW and EW, the greatest isolation frequency (p < 0.05) was recorded for the capitis/warneri group. The remaining six groups were isolated infrequently and in low numbers. DISCUSSION: These results show that, in addition to Staphylococcus epidermidis, other staphylococcal species may be important members of the normal microbiota of the ocular surface during SCL wear. Furthermore, an increase and a shift in staphylococcal microbiota between DW and EW regimes was highlighted.

Ovarian morphology and endocrine characteristics of female sheep fetuses that are heterozygous or homozygous for the inverdale prolificacy gene (fecX1).

The Inverdale gene (fecX1), located on the X chromosome, is a major gene affecting the ovulation rate of sheep. At each ovulation, ewes heterozygous (I+) for the fecX1 gene ovulate, on average, one more egg than noncarriers (++), whereas ewes that are homozygous (II) for this gene are infertile and have "streak" ovaries. Since formation of the ovary occurs in fetal life, it is possible that the fecX1 gene influences ovarian development before birth. The aims of this study were to examine the effects of the fecX1 gene on germ cell development, follicular formation and growth, and plasma gonadotropin concentrations at 5 different days of gestation (i.e., Days 40, 90, 105, 120, and 135) and also in adult life. The results suggest that one copy of the X-linked mutation in female fetuses leads to a retardation of germ cell development at Days 40 and 90 of gestation. However, from Day 105 of gestation, follicular formation and growth appear normal. By contrast, in females with two copies of the X-linked mutation, germ cell development and follicular formation appear normal, but thereafter follicular growth from the primary stage of development is impaired. During fetal life the plasma concentrations of FSH and LH, although not measurable at Day 40, were similar between all the genotypes at Day 105, 120, and 135 of gestation. The only exception was for LH at Day 90 in the I+ and II animals: in ewes with these genotypes the plasma concentrations of LH were similar but significantly lower (p < 0.01) than in the ++ genotype. In adult animals the plasma concentrations of FSH and LH were not different between the ++ and I+ genotypes, reflecting similar levels of ovarian follicular activity. However, in adult II animals, the plasma concentrations of FSH and LH were significantly higher (both p < 0.01) than in the ++ and I+ genotypes, reflecting the absence of normal secondary and antral follicles. In summary, these data show that the fecX1 gene affects ovarian development before birth and that the nature of the effect is influenced by whether the female fetus is a homozygous or heterozygous carrier of the X-linked mutation.

Evaluation of image quality using 1 : 1 pitch and 1.5 : 1 pitch helical CT in children: a comparative study.

OBJECTIVE: The objective of this study was to compare the quality of 1 : 1 and 1.5 : 1 pitch helical contrast-enhanced thoracic and abdominal CT images in children who cannot cooperate for breath holding. MATERIALS AND METHODS: This is a retrospective study of 33 contrast-enhanced CT examinations in 11 children of 0-4 years of age. All children had an initial CT study using 1 : 1 pitch helical scanning followed over the next 6-36 months by one to four CT examinations with 1.5 : 1 pitch. Radiation dose with the two techniques was measured with a pencil ionization chamber. RESULTS: The two techniques provided comparable overall image quality. There was 33 % less radiation dose with 1.5 : 1 pitch helical scanning. CONCLUSION: The 1.5 : 1 pitch helical CT provides comparable quality images and a smaller radiation dose than 1 : 1 pitch in examining children aged 0-4 years.

Effects of the Booroola gene (FecB(B)) on bodymass, testis development and hormone concentrations during fetal life.

In female fetuses the Booroola gene (FecB(B)) is known to affect germ cell development and consequently the pattern of ovarian follicular growth during fetal and post-natal life. However in males, the role of this gene during fetal development is unknown. The aims of the study reported here were to examine the effects of the FecB(B) gene on development of male fetuses with respect to body and organ mass for example, pituitary gland, adrenal and mesonephros), testes development, including numbers of germ cells, and also the plasma concentrations or tissue contents of the reproductive hormones (FSH, LH and testosterone) at days 40, 55, 75, 90 and 135 of gestation. The FecB(B) gene was found to influence litter size, bodymass, crown-rump length and testis mass at most stages of gestation. Some effects were also noted on the mesonephros at days 40 and 55 and on the pituitary and adrenal at days 90 or 135 of gestation. However, the FecB(B) gene was not observed to have an effect on the patterns of germ cell development, on pituitary content or plasma concentrations of immunoreactive or bioactive FSH or immunoreactive LH or testicular content of testosterone. When embryo transfer experiments were performed to eliminate the effects of litter size at days 40, 90 and 135 of gestation nearly all of the differences in bodymass, crown-rump length and organ mass disappeared. The only exception to this was at day 90 when bodymass continued to be lighter and crown-rump lengths smaller in the BB/B + fetuses compared with the +2 fetuses; the significance of this finding remains unknown. It is concluded that for Booroola male fetuses there are no direct effects of the FecB(B) gene on pituitary gonadotrophin function or testicular development after sexual differentiation. Moreover, although there may be temporal differences around day 90 of gestation, there are no long-term, direct effects of the FecB(B) gene on total body, adrenal, testis or pituitary mass. Collectively these findings for the male are similar to those for female fetuses except with regard to germ cell development.

Radiation design and control features of a hospital room for a low dose rate remote afterloading unit.

We have renovated, and used for four years, a small 3.4 m x 4.3 m conventional patient second floor hospital room to accommodate a low dose rate remote afterloading unit containing 13 GBq (0.35 Ci) of 137Cs. Supplemental room shielding consists of a power assisted door (536 kg, 1.7 cm thickness of lead), 1.3 cm lead wall shielding at selected wall locations and on a projector shield beneath the bed, and 0.6 cm of lead over the floor above. Radiation control features consisted of a room interior radiation detector independent of the remote afterloading unit, a redundant patient/nurse communication system, a remote control system, a door interlock system to insert and retract the radioactive pellets, and a visible and audible status indicator system located at a nearby nurses' work station. Renovation costs (in 1990 dollars) were $383 per square foot; total project costs were $187,000. Nursing personnel radiation exposure was reduced from about 6 microSv (mg Ra eq)-1 (0.6 mrem (mg Ra eq)-1) to about 0.7 microSv (mg Ra eq)-1 (0.07 mrem (mg Ra eq)-1, almost a tenfold reduction.

Dynamic contrast-enhanced MR imaging of fibrolamellar hepatocellular carcinoma.

The magnetic resonance (MR) appearance of fibrolamellar hepatocellular carcinoma (FL-HCC) on T1- and T2-weighted and dynamic serial postgadolinium-DTPA images is reported. Both tumors were large (> 7 cm in shortest dimension) and had central regions of low signal intensity on T1- and T2-weighted images. Diffuse heterogeneous enhancement of the tumors occurred on immediate postcontrast images. Lesions became more homogeneous in enhancement over time, but lack of enhancement of central portions of the tumor persisted. Although persistent lack of enhancement of the tumor scar on late postcontrast MR images may be characteristic of FL-HCC compared with delayed enhancement in focal nodular hyperplasia, the potential similarities between these tumors is stressed.

Installation of 60Co 100 cm source-to-axis distance teletherapy units in vaults designed for 80-cm units.

60Co teletherapy units featuring 100 cm source-to-axis distances and with nominal source activities of 481 TBq (13,000 Ci) are available as replacements for older model 80 cm source-to-axis teletherapy units that generally have source activities of less than 370 TBq (10,000 Ci). We have redesigned and renovated two vaults--one of which required supplemental shielding--designed for older 80 cm source-to-axis units with 333 TBq (9,000 Ci) sources and installed modern 100 cm source-to-axis units with 481 TBq (13,000 Ci) sources. Renovation costs (in 1991 U.S. dollars) were about $40,000 and $160,000; the latter, including shielding costs, was about two-thirds of projected costs for installation of a 6 MV electron beam linear accelerator (linac). We have designed the treatment heads of these 100 cm 60Co units to accept the secondary field shaping blocks used on 100 cm source-to-axis linacs, allowing the 60Co units to be used as emergency back-up units for linacs when they are inoperable.

Ontogeny of ovarian follicle development in Booroola sheep fetuses that are homozygous carriers or non-carriers of the FecB gene.

The aims of this study were to examine the effects of the Booroola FecB gene on ovarian development and reproductive hormones (FSH, LH and inhibin) at days 90, 100, 120 and 135 of gestation (term = 147 days). The effects of litter size were eliminated by transferring equal numbers of homozygous BB and control (++) embryos to recipient ewes. The ovary, but not the body, pituitary, adrenal, kidney or thymus, was heavier (P < 0.05) in BB compared with ++ fetuses at day 90 but not thereafter. In the ovary, gene-specific differences were observed in the total number of germ cells present at days 90 (P < 0.01) and 135 (P < 0.05) with the same tendency being noted at day 100 (P < 0.07); at all of these ages the mean numbers of germ cells in the BB genotype exceeded those in ++ animals. Gene-specific differences were observed in the numbers of oogonia and isolated oocytes at day 90 (i.e. BB > ++), in the number of primordial follicles at days 100 (BB > ++) and 135 (BB > ++), and also in the number of primary or secondary follicles (++ > BB) at day 135. At each gestational age examined no differences were noted with respect to the plasma concentrations of FSH, LH or inhibin between the BB and ++ fetuses. However, the highest mean plasma concentrations of FSH and LH occurred at days 90 and 100 of gestation, which coincided with the first developing primary follicles.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal corticomedullary differentiation: observation in patients with differing serum creatinine levels.

PURPOSE: To evaluate renal corticomedullary differentiation (CMD) in patients with differing serum creatinine (sCr) levels. MATERIALS AND METHODS: Ten patients with normal sCr levels (0.9-1.3 mg/dL [80-115 mumol/L]), 14 with mildly elevated levels (1.5-2.9 mg/dL [133-256 mumol/L]), and 15 with elevated levels (> 3.0 mg/dL [265 mumol/L]) were examined with unenhanced T1-weighted fat-suppressed spin-echo (T1FS) and immediate gadolinium-enhanced gradient-echo (Gd-GRE) imaging. RESULTS: Patients with normal sCr levels had CMD on T1FS and Gd-GRE images. Among patients with mildly elevated levels, seven did and seven did not have CMD on T1FS images; all had CMD on Gd-GRE images. Patients with elevated levels had no CMD on T1FS images; 13 had CMD on Gd-GRE images. Two patients with levels above 10.0 mg/dL (884 mumol/L) had no CMD on Gd-GRE images. CONCLUSION: Independent of the cause of elevated sCr level, levels above 3.0 mg/dL result in loss of CMD on T1FS images, while levels above 10.0 mg/dL result in loss of CMD on Gd-GRE images.

Effect of outer membrane of Treponema denticola on bone resorption.

The effect of the outer membrane (outer sheath) of Treponema denticola on bone resorption was studied. Bone resorption was measured by the release of previously incorporated 45Ca from the shafts of the radii and ulnae of 19-day fetal rats. A treated-over-control ratio (T/C ratio) significantly greater than 1 indicated the stimulation of bone resorption by the test substance. The addition of outer membrane of T. denticola increased the release of 45Ca from the assay bones. The minimum concentrations required to yield significant 45Ca release from the assay bones were 15, 22 and 75 micrograms protein/ml for serovars a, b and c, respectively. These protein values corresponded to estimated lipopolysaccharide contents of 0.6, 0.8 and 2.8 micrograms/ml, based on 3-deoxy-2-manno-octulosonate analysis. Heat treatment of outer membrane (60 degrees for 30 min) did not change the effect on 45Ca release. Parathyroid hormone or prostaglandin E2, known to act synergistically with lipopolysaccharides in bone resorption, was also added to the assay system. Neither prostaglandin E2 at 10(-7) M nor parathyroid hormone at 40 ng/ml, by itself, increased 45Ca release. However, in the presence of 10 micrograms protein/ml of outer membrane of serovar b at 120 h, the T/C ratio was increased to 1.31 +/- 0.07 and 1.58 +/- 0.118, respectively. These results suggest that a lipopolysaccharide-like material is present in the outer membrane of T. denticola that may be responsible for bone resorption in the in vitro system.

Phosphorylated nutrient uptake by Treponema denticola and other potential periodontopathogens.

Nutrient uptake may contribute to the survival of certain potential periodontopathogens in the competitive environment of the gingival sulcus. This study was conducted to assess the uptake of commercially available, key radiolabelled phosphorylated compounds by Treponema denticola. There was a linear relationship in the uptake of ATP and G-1-P with cell concentrations of 0.1-2.5 mg of cell dry weight. This uptake reached a steady state within 15 min, and at temperatures of 25-37 degrees C the uptake ranged between 13-21%. At 50 degrees C, or above 50 degrees C the assay cells took up 0-1% of the assay nutrients. The maximum uptake of ATP was 47.5, 38 and 47.6 pmoles for serovars a, b and c. G-1-P yielded maximum uptake values of 306, 304, and 306 pmoles respectively. Significant uptake of ATP, or G-1-P occurred at pH 4.8 for serovars a, or c, while serovar b showed a broad pH range for the uptake of G-1-P. Stannous fluoride at a concentration of 0.17 mM enhanced the uptake of ATP while chlorhexidine digluconate inhibited the uptake of ATP. At concentrations usually employed (0.05-0.5 mM) the metabolic poisons 2,4-dinitrophenol, sodium azide, sodium arsenite and the ATPase inhibitor N,N1-dicyclohexylcarbodiimide did not alter significantly the uptake of ATP. The uptake of ATP, by Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Fusobacterium nucleatum and T. denticola at pH 4.8 was 13.4, 1.5, 6.9, and 18-20.4%, respectively. At pH 6.5 the uptake for the microorganisms indicated above was 22, 1.3, 6.6 and 6.2%, respectively. G-1-P showed the same trend in its uptake by A. actinomycetemcomitans, P. gingivalis, F. nucleatum and T. denticola. This study provides for the first time specific examples of phosphorylated nutrient uptake by potential periodontopathogens, and that the uptake of phosphorylated nutrients can be suppressed by oral hygienic compounds.

Corticosteroid therapy for chronic obstructive pulmonary disease. Is it worth the risks?

The majority of patients with chronic obstructive pulmonary disease (COPD) do not appear to benefit from long-term corticosteroid therapy. Nevertheless, a small minority demonstrate a response to treatment that is so dramatic that it may be worth the risk of chronic corticosteroid use. A corticosteroid trial is indicated in the patient with COPD who remains symptomatic despite adequate and aggressive routine treatment. If substantial improvement is noted in pulmonary function, chronic corticosteroid treatment should be considered. In patients without an objective response, long-term corticosteroid therapy should not be continued.