John A. Gonzales

Human papillomavirus infection in sexually active adolescent females: prevalence and risk factors.

ABSTRACT: We examined the prevalence of human papillomavirus (HPV) infection, and associated risk factors for infection with HPV types 6,11,16,18, 31, 33, and 35, in 661 sexually active adolescent females attending family planning clinics. Fifteen percent were positive for HPV DNA by RNA-DNA dot-blot hybridization. More than 60% of the HPV-positive subjects harbored at least one of the following cancer-related HPV types: 16, 18, 31, 33, or 35. Those with HPV had a mean range of four to 10 lifetime sexual partners compared with a mean range of one to three in those without HPV (p < 0.001). After the analysis was adjusted for number of lifetime sexual partners, no other risk factor was associated with HPV infection. We conclude that oncogenic-related HPV types are common sexually transmitted organisms found in our population. The strong relationship with number of sexual partners suggests that acquisition of HPV infection is predominantly influenced by sexual behavior. However, in our population, confounders such as oral contraceptive use, past history of Chlamydia trachomatis infection, or substance abuse were not found to be significant independent risk factors.

Natural history of anal cytologic abnormalities and papillomavirus infection among homosexual men with group IV HIV disease.

Previous studies have demonstrated a high prevalence of anal cytologic abnormalities as well as anal human papillomavirus (HPV) infection among homosexual men with group IV HIV disease. However, the natural history of these changes in this population has not yet been studied. To this end, 37 homosexual men with group IV HIV disease attending an outpatient HIV clinic were followed at approximately 9-month intervals for an average of 17 months, using anal cytology, anoscopy, anal biopsy, and anal HPV DNA hybridization. During the study, the proportion of the 37 subjects with anal cytologic abnormalities increased from 27 to 65%. The proportion of subjects with any grade of anal intraepithelial neoplasia rose from 8 to 32%, with high-grade anal intraepithelial neoplasia increasing from 0 to 16%. The proportion of subjects with anal HPV infection increased from 60 to 89%, and infection with multiple HPV types was noted in at least 48%. We conclude that a large proportion of homosexual men with group IV HIV disease develop anal cytologic abnormalities, including anal intraepithelial neoplasia, over a short period of time. Together with a rapidly increasing incidence of anal cancer among single, never-married men in the San Francisco Bay area, these results suggest that these men may be at significant risk of development of anal cancer.

Biopsy techniques and yields in diagnosing primary intraocular lymphoma

A review of current biopsy techniques that are used in obtaining specimens from which to make a diagnosis of primary intraocular lymphoma (PIOL) is presented. Methods for obtaining and subsequently testing vitrectomy specimens are discussed. In addition, the yields of external and internal approaches for obtaining chorioretinal tissue, and diagnostic vitrectomies, are reviewed.

Lamellar bodies of cultured human fetal lung: Content of surfactant protein A (SP-A), surface film formation and structural transformation in vitro

Lamellar bodies were isolated from dexamethasone and T3-treated explant cultures of human fetal lung, using sucrose density-gradient centrifugation. We examined their content of surfactant apoprotein A (SP-A), and their ability to form surface films and to undergo structural transformation in vitro. SP-A measured by ELISA composed less than 2% of total protein within lamellar bodies; this represented, as a minimum estimate, a 2-12-fold enrichment over homogenate. One- and two-dimensional gel electrophoresis also suggested that SP-A was a minor protein component of lamellar bodies. Adsorption of lamellar bodies to an air/water interface was moderately rapid, but accelerated dramatically upon addition of exogenous SP-A in ratios of 1:2-16 (SP-A:phospholipid, w/w). Similar adsorption patterns were seen for lamellar bodies from fresh adult rat and rabbit lung. Lamellar bodies incubated under conditions that promote formation of tubular myelin underwent structural rearrangement only in the presence of exogenous SP-A, with extensive formation of multilamellate whorls of lipid bilayers (but no classical tubular myelin lattices). We conclude that lamellar bodies are enriched in SP-A, but have insufficient content of SP-A for structural transformation to tubular myelin and rapid surface film formation in vitro.

Glucocorticoid stimulation of fatty acid synthesis in explants of human fetal lung

We examined the effects of glucocorticoids and thyroid hormone (T3) on fatty acid synthesis, fatty acid composition and fatty acid synthetase activity in explants of human fetal lung (16-23 wk gestation). Explants were cultured 1-7 days in the absence (control) or presence of dexamethasone (10 nM) and/or T3 (2 nM). In control explants fatty acid synthesis and fatty acid synthetase activity increased 200% and 455%, respectively, between 1 and 5 days. Dexamethasone (10 nM) stimulated fatty acid synthesis (tritiated water incorporation) 155% and fatty acid synthetase activity 117% after 5 days in culture. T3 (2 nM) was not stimulatory, either alone or in the presence of dexamethasone. Dexamethasone increased the proportion of newly synthesized fatty acid recovered in phosphatidylcholine from 72% (control) to 90% (P less than 0.02) of total fatty acid. Dexamethasone stimulation of fatty acid synthetase activity was consistent with a receptor-mediated process: (1) stimulation was saturable and dose-dependent (Kd = 1.5 +/- 0.3 nM); (2) the potency of glucocorticoid analogs and other steroids reflected their glucocorticoid activity; (3) stimulation was reversible when cortisol was removed from the medium. Stimulation by dexamethasone was apparent within 24 h of hormone exposure, and increased to a maximum between 4 and 6 days. Fatty acid synthetase activity was higher in Type II cells (3.54 +/- 0.58 nmol malate/min per mg protein) than in fibroblasts from treated explants. Although both cell types responded to hormone treatment the stimulation was greater for Type II cells (200% vs. 75% increase). The fatty acid composition of PC showed increases in 14:0 and 16:1 with culture alone which were further stimulated by dexamethasone but not T3. These results indicate glucocorticoid stimulation of fatty acid synthesis and are consistent with a key role for fatty acid synthetase in the hormonal induction of pulmonary surfactant phosphatidylcholine synthesis in cultured fetal lung.

Congenital torticollis: evaluation by fine-needle aspiration biopsy.

Fine‐needle aspiration biopsy, used extensively for evaluating head and neck masses in adults, also provides an excellent minimally invasive means of evaluating infants with neck masses and torticollis. Three cases of torticollis involving infants are presented. In each case, fine‐needle aspiration revealed a benign fibrous lesion, ruling out malignancy. The remaining cytologic differential diagnosis between infantile fibromatosis, fibromatosis colli, and calcifying aponeurotic fibrosis is discussed, with mention of the possible causes of and treatment for congenital torticollis. We conclude that fine‐needle aspiration provides a fast and accurate diagnosis of neck masses in infants who have congenital torticollis, thereby avoiding surgical procedures in this very young age group.

Association Between Atopy and Herpetic Eye Disease: Results From the Pacific Ocular Inflammation Study

IMPORTANCE Immune dysregulation in patients with atopy has been hypothesized to increase susceptibility to viral infections. Herpetic eye disease (due to herpes simplex and herpes zoster) is a significant cause of visual impairment, and data on an association between this sight-threatening disease and atopy are limited. OBJECTIVE To assess the association between atopy and herpetic eye disease, including herpes simplex virus (HSV) ocular disease and herpes zoster ophthalmicus (HZO). DESIGN, SETTING, AND PARTICIPANTS Retrospective, population-based case-control study from January 1, 2006, through December 31, 2007, at Kaiser Permanente Hawaii, a multispecialty managed care organization serving approximately 15% of the general Hawaiian population. Participants were 217,061 patients enrolled in the Kaiser Permanente Hawaii health plan during the study period. MAIN OUTCOMES AND MEASURES Clinical diagnosis of HSV ocular disease or HZO during the study period determined by an initial search of the electronic medical record of Kaiser Permanente Hawaii and then confirmed through individual medical record review by a uveitis and cornea fellowship-trained ophthalmologist. Atopic disease status was determined based on International Classification of Diseases, Ninth Revision codes for patients with HSV ocular disease or HZO and 2 control groups, each randomly selected at a 4:1 ratio of controls to cases. RESULTS One hundred fourteen patients with HSV ocular disease and 137 patients with HZO were identified. Using the age- and sex-matched controls, patients who had atopy had a 2.6-fold (95% CI, 1.6-4.2; P < .001) higher odds of having HSV ocular disease compared with patients who did not have atopy. Similarly, patients with atopy had a 1.8-fold (95% CI, 1.2-2.8; P = .01) increased odds of having HZO. Patients with 2 or more atopic conditions had an 8.9-fold (95% CI, 3.5-22.6; P < .001) higher odds of having HSV ocular disease and a 2.9-fold (95% CI, 1.1-7.7; P = .04) higher odds of having HZO. CONCLUSIONS AND RELEVANCE The association between atopy and herpetic eye disease may be explained by various factors, including immunologic dysfunction in patients with atopy. Clinically, these results could help support the diagnosis of herpetic eye disease in these patients.

The association between human papillomavirus deoxyribonucleic acid status and the results of cytologic rescreening tests in young, sexually active women

We examined the utility of cytologic rescreening tests in women who had positive test results for human papillomavirus deoxyribonucleic acid but who were diagnosed as having benign conditions at cytologic testing. One hundred twenty-five Papanicolaou smears from women who were screened for human papillomavirus deoxyribonucleic acid were sent routinely to a private laboratory for diagnoses. These slides were then reviewed independently by two pathologists who were blinded to the human papillomavirus deoxyribonucleic acid results. The effects of cytologic rescreening in cases of both positive and negative human papillomavirus deoxyribonucleic acid were assessed by calculating z scores. Cervical intraepithelial neoplasia was diagnosed in 40% by pathologist A and in 20% by pathologist B of the human papillomavirus-positive subjects compared with none diagnosed by the private cytology laboratory (z = 3.09, p less than 0.005 and z = 1.98, p less than 0.05, respectively). No significant differences were found in the human papillomavirus-negative group. We conclude that cytologic rescreening in human papillomavirus deoxyribonucleic acid-positive women who were initially diagnosed as having benign cytologic results will yield a significant proportion of cases of cervical intraepithelial neoplasia.

Multimodal imaging of white and dark without pressure fundus lesions.

Purpose: To describe multimodal imaging findings in patients with dark or white without pressure lesions of the fundus. Methods: Retrospective observational case series of 10 patients with white or dark without pressure lesions. We analyzed multimodal imaging using spectral domain optical coherence tomography, color and near-infrared fundus photography, and fundus autofluorescence imaging to explore the findings associated with these lesions. Results: All patients had geographic dark or white lesions on clinical examination and color photography, which were either hyporeflective or hyperreflective on near-infrared reflectance imaging, respectively. On optical coherence tomography, these lesions correlated with an abrupt change of the photoreceptor reflectivity, with relative hyporeflectivity of photoreceptor zones (ellipsoid and interdigitation zones, as well as outer segments) within the dark, and relative hyperreflectivity within white lesions. Ten patients underwent fundus autofluorescence, which showed well-defined zones of relative hypo-autofluorescence within the lesion, compared with neighboring uninvolved regions, whether dark or white without pressure. In two patients who had a lesion combining white and dark without pressure, we observed the transition in photoreceptor reflectivity from the dark lesion (hyporeflective) to the white lesion (hyperreflective), relative to the surrounding retina. Conclusion: Both white and dark without pressure lesions are associated with changes in outer retinal reflectivity on optical coherence tomography, which occur in opposite directions compared with the surrounding unaffected areas. In the face of normal visual field testing to date, the clinical significance of this finding remains uncertain. Recognition of the optical coherence tomography appearance will help clinicians avoid unnecessary workup of these patients for outer retinal dystrophy or degeneration.

Visual loss associated with tacrolimus: case report and review of the literature

Tacrolimus is an immunosuppressive medication in the class of calcineurin inhibitors that acts by inhibiting T-cell and interleukin-2 activity, and is commonly used after allogeneic organ transplant. We present a patient who used tacrolimus after cadaveric kidney transplant and experienced blurry vision. Ocular examination and patient’s course subsequently revealed aqueous tear deficiency as a dose-dependent adverse effect of oral tacrolimus.