Masquerade syndrome: sebaceous carcinoma presenting as an unknown primary with pagetoid spread to the nasal cavity

Sebaceous carcinoma of the eyelid is an uncommon tumour with unusual modes of presentation. It can remain occult at the primary site, without producing any mass, masquerading as chronic blepharoconjunctivitis, while setting up metastases in the regional lymph nodes especially in the pre-auricular group. We report here a case that not only masqueraded as chronic blepharoconjunctivitis with nodal metastases from an 'unknown primary' in the neck, but whose tumour spread in a pagetoid manner along the nasolacrimal duct producing a nasal tumour that was believed to be the 'unknown primary'. This case emphasizes the need for ophthalmologists, ENT surgeons and pathologists to keep sebaceous carcinoma in mind while evaluating patients with chronic blepharoconjunctivitis and cervical node metastases from 'unknown primary'. Histological clues for picking up a sebaceous carcinoma at a metastatic site include a tumour with comedo or ductal growth pattern and intracytoplasmic lipid.     

Evaluation of endometrial steroid receptors and cell mitotic activity in women using copper intrauterine device: Can Cu-T prevent endometrial cancer?

AIMS: To study changes in endometrial proliferative indices (i.e. cell mitosis and Ki67), endometrial steroid (estrogen and progesterone) receptors, and serum estradiol and progesterone level in women using copper intrauterine device (IUD) after 6 months of use. METHODS: Fifteen healthy women were recruited having no contra indication to IUD or endometrial biopsy. Endometrial biopsies and serum samples were taken on 10/11th day of menstrual cycle at recruitment and after six months. The endometrial samples were subjected to: (i) steroid receptor estimation by immunohistochemistry; (ii) cell mitosis and Ki67 estimation by morphology and proliferative indices. RESULTS: The mean glandular mitotic index was 1.69 +/- (0.39) at first visit and 0.35 +/- (0.15) at second visit after 6 months. Similarly, Ki-67 count in glands was 11.79 +/- (1.59) at first visit and 2.40 +/- (0.54) at second visit. In the stroma, Ki67 decreased from a mean of 0.85 to 0.01 in six months. This suggested statistically significant reduction in proliferation and mitotic activity in endometrial glands and the stroma of women who used Cu-T continuously for a long period.There was a significant reduction of estrogen receptor concentration in glands (from a mean of 51.67 down to 11.67) and the stroma (from a mean of 33.00 to 8.00) over this 6-month period. The observed fall in progesterone receptor counts was less compared to other parameters studied, being marginally significant in stroma (from a mean of 32.00 down to 14.33), but not significant enough in glands (from a mean of 45.00 down to 25.00). No changes were observed in serum hormone levels in these two visits. CONCLUSION: Continuous use of copper intrauterine device causes significant reduction in endometrial mitotic activity as well as estrogen receptor concentration without affecting serum estradiol or progesterone levels. This finding infers that Cu-T may have a protective role against endometrial cancer.     

Determination of both the time constant of vO2 and DeltavO2/DeltaW from a single incremental exercise test: validation and repeatability

A single incremental cycle exercise test including a steady-state load, combined with respiratory gas exchange, was performed with the objective of determining the time constant (tauVO(2)) and the amount of oxygen required at each load (DeltaVO(2)/DeltaW) by using a novel equation. The protocol was validated using four exercise tests at different constant loads and conventionally fitted mono-exponential functions to determine tauVO(2), and interpolation of VO(2) versus load to determine DeltaVO(2)/DeltaW. No significant differences were seen between the means of either tauVO(2) or DeltaVO(2)/DeltaW determined with the two protocols. The correlation coefficient was 0.62 for tauVO(2) and 0.48 for DeltaVO(2)/DeltaW. The absolute differences (2 SD) were 11.6 s for tauVO(2) and 1.1 ml min(-1) W(-1) for DeltaVO(2)/DeltaW. The equations were compared in the same steady-state test and good agreement of tauVO(2) was obtained (R = 0.99). The 5-6-week repeatability (incremental test) was evaluated. No statistical differences were seen between the mean of the repeated tests. The difference between the tests (2 SD) were 20 s for tauVO(2) and 1.2 ml min(-1) W(-1) for DeltaVO(2)/DeltaW. In conclusion, tauVO(2) and DeltaVO(2)/DeltaW can be determined from a single incremental test. The validation showed an acceptable agreement, although the variations in absolute values were not negligible. This could partly be explained by the natural day-to-day variation and fluctuations in incoming raw data. The test-retest variation in absolute values was considerable, which must be taken into account when using tauVO(2) and DeltaVO(2)/DeltaW for evaluation of aerobic function.     

A multiple-dose phase I study of intranasal hydromorphone hydrochloride in healthy volunteers

We evaluated the pharmacokinetics, tolerability, and safety of 1 and 2 mg of intranasal hydromorphone hydrochloride in an open-label, single- and multiple-dose study. This Phase I study was conducted in 24 healthy volunteers (13 men and 11 women). Intranasal doses were delivered as 0.1-mL metered-dose sprays into one or both nostrils for 1- and 2-mg doses, respectively. Venous blood samples were taken serially from 0 to 12 h after the first single dose and the last (seventh) multiple dose. Plasma hydromorphone concentrations were determined by liquid chromatography/mass spectrometry/mass spectrometry. Noncompartmental analysis was used to estimate pharmacokinetic variables. After 7 intranasal doses of 1 and 2 mg (once every 6 h), mean +/- sd peak plasma concentrations of 2.8 +/- 0.7 ng/mL and 5.3 +/- 2.3 ng/mL, respectively, were observed. The median time to peak concentration was 20 min for both single and multiple doses. Dose proportionality was observed for the 1- and 2-mg doses. Adverse events included somnolence, dizziness, and bad taste after dose administration. Intranasal hydromorphone hydrochloride was well tolerated and demonstrated rapid nasal drug absorption and predictable accumulation. These results support clinical investigation of hydromorphone hydrochloride nasal spray for use as an alternative to oral and IM administration.     

A simple technique to reduce epistaxis and nasopharyngeal trauma during nasotracheal intubation in a child with factor IX deficiency having dental restoration

Epistaxis and airway trauma are often associated with nasotracheal intubation. We describe a patient with Factor IX deficiency who required nasotracheal intubation. An inexpensive, nonproprietary, rapid technique was used to reduce the trauma of intubation.     

Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome

BACKGROUND: Nephrotic syndrome (NS) represents the association of proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Steroid-resistant nephrotic syndrome (SRNS) is defined by primary resistance to standard steroid therapy. It remains one of the most intractable causes for end-stage renal disease (ESRD) in the first two decades of life. Sporadic mutations in the Wilms' tumor suppressor gene WT1 have been found to be present in patients with SRNS in association with Wilms' tumor (WT) and urinary or genital malformations, as well as in patients with isolated SRNS. METHODS: To further evaluate the incidence of WT1 mutations in patients with NS we performed mutational analysis in 115 sporadic cases of SRNS and in 110 sporadic cases of steroid-sensitive nephrotic syndrome (SSNS) as a control group. Sixty out of 115 (52%) patients with sporadic SRNS were male, 55/115 (48%) were female. Sex genotype was verified by haplotype analysis. Mutational analysis was performed by direct sequencing and by denaturing high-performance liquid chromatography (DHPLC). RESULTS: Mutations in WT1 were found in 3/60 (5%) male (sex genotype) cases and 5/55 (9%) female (sex genotype) cases of sporadic SRNS, and 0/110 (0%) sporadic cases of SSNS. One out of five female patients with mutations in WT1 developed a WT, 2/3 male patients presented with the association of urinary and genital malformations, 1/3 male patients presented with sexual reversal (female phenotype) and bilateral gonadoblastoma, and 4/5 female patients presented with isolated SRNS. CONCLUSION: According to the data acquired in this study, patients presenting with a female phenotype and SRNS and male patients presenting with genital abnormalities should especially be screened to take advantage of the important genetic information on potential Wilms' tumor risk and differential therapy. This will also help to provide more data on the phenotype/genotype correlation in this patient population.