Clinical characteristic and management of haemophilia patients in Malaysia: A single centre experience.

INTRODUCTION: Haemophilia is one of the commonest inherited bleeding disorders which may lead to long term disabilities if not treated properly. Our aim of study is to understand the clinical characteristic, treatment and complications of adult haemophilia patients in our centre. MATERIALS AND METHODS: A retrospective cross-sectional review of all adult haemophilia A (HA) or haemophilia B (HB) patients who received treatment in Hospital Pulau Pinang from January 2021 to December 2022 was conducted. Data was retrieved from patients' medical records. RESULTS: A total of 75 haemophilia patients (64 HA and 11 HB) were included in this study with median age of 37 years (range 19 70). 42 of them had severe haemophilia (50% of HA, 91% of HB). All HB and 93.8% of severe HA patients were on prophylaxis. Six severe and one mild HA patients developed inhibitor with four of them currently on non-factor prophylaxis. 24 patients (32%) had prior hepatitis C infection and all of them have been successfully treated. The mean annual bleeding rate for severe haemophilia patients were 1.77 (SD ±3.6). Target joints were observed in 9.3% of patients with ankle joint (71.4%) being the most affected joint. More than one quarter (26.7%) of our patients have comorbidities with majority of them having hypertension (17/20), followed by diabetes mellitus (5/20) and ischemic heart disease (5/20). CONCLUSION: Our study showed that a significant number of adult patients with haemophilia have comorbidities. Apart from optimising factor replacement therapy, future planning should include improvement in screening, risk modification and prevention of cardiovascular disease.

Matrix Matters: Assessment of Commutability among BK Virus Assays and Standards.

Quantitative testing of BK virus (BKPyV) nucleic acid has become the standard of care in transplant patients. While the relationship between interassay harmonization and commutability has been well characterized for other transplant-related viruses, it has been less well studied for BKPyV, particularly regarding differences in commutability between matrices. Here, interassay agreement was evaluated among six real-time nucleic acid amplification tests (NAATs) and one digital PCR (dPCR) BKPyV assay. Differences in the commutability of three quantitative standards was examined across all assays using a variety of statistical approaches. Panels, including 40 samples each of plasma and urine samples previously positive for BKPyV, together with one previously negative plasma sample and four previously negative urine samples, were tested using all assays, with each real-time NAAT utilizing its usual quantitative calibrators. Serial dilutions of WHO, National Institute for Standards and Technology (NIST), and commercially produced (Exact/Bio-Rad) reference materials were also run by each assay as unknowns. The agreement of the clinical sample values was assessed as a group and in a pairwise manner. The commutability was estimated using both relativistic and quantitative means. The quantitative agreement across assays in the urine samples was within a single log10 unit across all assays, while the results from the plasma samples varied by 2 to 3 log10 IU/mL. The commutability showed a similar disparity between the matrices. Recalibration using international standards diminished the resulting discrepancies in some but not all cases. Differences in the sample matrix can affect the commutability and interassay agreement of quantitative BKPyV assays. Differences in commutability between matrices may largely be due to factors other than those such as amplicon size, previously described as important in the case of cytomegalovirus. Continued efforts to standardize viral load measurements must address multiple sources of variability and account for differences in assay systems, quantitative standards, and sample matrices.

Building pharmacogenetics into a pharmacovigilance program in Singapore: using serious skin rash as a pilot study.

To study the possible genetic associations with adverse drug reactions (ADR), the Singapore Health Sciences Authority (HSA) has piloted a program to collect DNA and phenotype data of ADR cases as part of its pharmacovigilance program. Between 2009 and 2012, HSA screened 158 cases of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). To assess the association between HLA-B*1502 and carbamazepine (CBZ)-induced SJS/TEN, 13 cases and 26 drug-tolerant controls were analyzed. All 13 CBZ-SJS/TEN cases and 3/26 controls were HLA-B*1502 positive (odds ratio 181, 95% confidence interval: 8.7-3785, P=6.9 × 10(-8)). Discussions of the finding with the Ministry of Health and an expert panel led to the decision to make HLA-B*1502 testing the standard of care prior to first use of CBZ in Asians and to subsidize the genotyping test at public hospitals. This program illustrates the role of a regulatory authority in advancing the use of pharmacogenetics for drug safety.

Emergency stenting of vertical vein in a neonate with obstructed supracardiac total anomalous pulmonary venous drainage.

A late preterm newborn baby presented with respiratory distress and increasing cyanosis within 2 hours of birth. Bedside transthroracic echocardiography showed a critically obstructed vertical vein in a supracardiac total anomalous pulmonary venous drainage (TAPVd). Emergency stenting of the vertical vein was successfully performed at 24 hours of life.

Carotid intima media thickness and high sensitivity C-reactive protein as markers of cardiovascular risk in a malaysian population.

INTRODUCTION: Carotid intima media thickness (CIMT) being a cost effective and easily performed technique is useful in the detection of subclinical atherosclerosis and has been shown to be a prognosticator of cardiovascular events. The primary objective of this study was to obtain the distribution of CIMT measurements, highly sensitive C reactive protein (hs-CRP) and assessing health awareness and attitudes of the Malaysian population at cardiovascular disease (CVD) risk and not receiving lipid lowering agents. Secondarily the study sought to assess the significance of the relationship between these measurements against various patient characteristics. METHODS: Measurements of CIMT are obtained by ultrasonography of 12 sites within the common carotid artery was recorded for 123 subjects from a single centre tertiary hospital of Malaysia who had two or more CVD risk factors but were not receiving lipid lowering therapy. CVD risk factors and lipid and glucose profiles were analyzed with respect to distribution of CIMT and high-sensitivity Creactive protein (hs-CRP) values. RESULTS: The mean-max CIMT was 0.916±0.129mm (minimum 0.630mm, maximum 1.28mm) and the mean-mean CIMT was 0.743±0.110mm (minimum 0.482mm, maximum 1.050mm) and mean hs-CRP was 0.191mg/dL (minimum 0.030mg/dL, maximum 5.440mg/dL). Multivariate analyses confirmed a significant association between increasing CIMT and increasing age, total and low density lipoprotein cholesterol while log-transformed hs-CRP levels showed significant association with increasing body mass index, waist circumference, high blood glucose and triglyceride levels. Our patients had good health awareness on CVD. CONCLUSION: Newly defined CIMT measurements and hs-CRP levels may be useful adjunctive tools to screen for atherosclerosis in the Malaysian population. It may help in refining risk stratification on top of traditional clinical assessment.

Gait improvement by high-frequency stimulation of the subthalamic nucleus in Parkinsonian mice is not associated with changes of the cholinergic system in the pedunculopontine nucleus.

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is standard care for severe motor symptoms of Parkinson's disease (PD). However, a challenge of DBS remains improving gait. Gait has been associated with the cholinergic system in the pedunculopontine nucleus (PPN). In this study, we investigated the effects of long-term intermittent bilateral STN-DBS on PPN cholinergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) Parkinsonian mouse model. Motor behavior, previously assessed by the automated Catwalk gait analysis, demonstrated a parkinsonian-like motor phenotype with static and dynamic gait impairments, which were reversed by STN-DBS. In this study, a subset of brains was further immunohistochemically processed for choline acetyltransferase (ChAT) and the neuronal activation marker c-Fos. MPTP treatment resulted in a significant reduction of PPN ChAT expressing neurons compared to saline treatment. STN-DBS did not alter the number of ChAT expressing neurons, nor the number of double-labelled PPN neurons for ChAT and c-Fos. Although STN-DBS improved gait in our model this was not associated with an altered expression or activation of PPN acetylcholine neurons. Motor and gait effects of STN-DBS are therefore less likely to be mediated by the STN-PPN connection and PPN cholinergic system.

Exogenous ochronosis in ethnic Chinese Asians: a clinicopathological study, diagnosis and treatment.

BACKGROUND: Exogenous ochronosis is believed to be an uncommon complication of treatment with hydroquinone- containing skin-lightning agents. It is widely believed that the condition is found almost exclusively in dark-skinned individuals and uncommon in other skin-types. AIMS: To show that exogenous ochronosis may be present in ethnic Chinese Asians. MATERIALS & METHODS: Facial skin biopsies were obtained from suspicious lesions in ethnic Chinese patients presenting at a private dermatology clinic. Clinical photographs, ultraviolet (UV) photographs and digital dermatoscopic pictures were also obtained. RESULTS: 15 patients of ethnic Chinese origin had histologically-confirmed exogenous ochronosis. DISCUSSION: The difficulties in differentiating exogenous ochronosis from melasma are discussed and there is a likelihood of under-reporting as the clinical presentation of the condition may be misleading. CONCLUSION: Exogenous ochronosis may exist amongst ethnic Chinese patients with fairer skin-types, contrary to the commonly-accepted perception that it is more prevalent in darker skin-types.

Controlled field studies on soil aquifer treatment in a constructed coastal sandfill.

A controlled artificial recharge experiment was conducted to investigate the effect of soil aquifer treatment during percolation of secondary and tertiary (ultrafiltered) treated wastewater through the shallow vadoze zone of a newly constructed coastal sandfill. The sandfill is a reclaimed land constructed from marine sand dredged from the seabed. To obtain 1-D flow, a stainless steel column was driven to a depth of 2.5 m, penetrating the phreatic surface. Wastewater was percolated through the column under fully-saturated and unsaturated conditions. Infiltration rates, dissolved organic carbon (DOC) and ultra-violet absorption (UVA) were monitored. The wastewaters were recharged at similar infiltration rates of approximately 5.5 m/day and 3.5 m/day under fully-saturated and unsaturated conditions, respectively. In both cases, clogging occurred 40 days after the start of recharge, under saturated conditions. For secondary treated wastewater, DOC concentration (mg/l) reduced by 28% and 13% under unsaturated and saturated conditions, respectively. The corresponding UVA reduction was 19.4% and 14.1%. Similar reductions in DOC were observed for the tertiary treated wastewater; however, the reduction in UVA was higher; 28% and 22% under unsaturated and saturated conditions, respectively. On an mass removal (mg/m(2) DOC) basis, DOC reduction appeared to be more significant under unsaturated conditions. This is attributed to the presence of interstitial oxygen.

Three-dimensional pharyngeal airway changes in dento-skeletal class II patients after two-jaw orthognathic surgery with segmentation - a pilot study.

PURPOSE: To investigate short- and long-term post-surgical three-dimensional changes of pharyngeal airway morphology and hyoid bone position in dento-skeletal class II deformity patients after two-jaw surgery with segmentation. METHODS: Relations between skeletal movement, hyoid bone position and three-dimensional pharyngeal airway changes were retrospectively analyzed on pre- and post-surgical CBCTs in dento-skeletal class II patients who underwent orthognathic two-jaw surgery with segmentation. RESULTS: While long-term significant reductions in length (P= 0.003), surface area (P= 0.042) and volume (P= 0.004) were found in the nasopharynx, the highly significant increases in oropharyngeal airway length, surface area, volume and the minimal cross-sectional area (P < 0.05) prevailed only in the short-term. Although a significant antero-superior movement of the hyoid bone was detected both in short- and long-term follow-up CBCTs (P < 0.05), only its superior, but not the anterior movement was found to be associated with an increased lateral width of the oropharyngeal minimal cross-sectional area. CONCLUSION: Two-jaw orthognathic surgery with segmentations in dento-skeletal class II patients improved oropharyngeal airway parameters significantly in the short-, but not long-term.

ARF and PITP restore GTP gamma S-stimulated protein secretion from cytosol-depleted HL60 cells by promoting PIP2 synthesis.

BACKGROUND: In many cell types, including neutrophils and HL60 cells, there is an absolute requirement for a GTP-dependent step to elicit Ca(2+)-regulated secretion. Neutrophils and HL60 cells secrete lysosomal enzymes from azurophilic granules; this secretion is inhibited by 1% ethanol, indicating that phosphatidate (PA) produced by phospholipase D (PLD) activity may be involved. PLD can use primary alcohols in preference to water during the hydrolytic step, generating the corresponding phosphatidylalcohol instead of PA, its normal product. As ARF (ADP-ribosylation factor) proteins regulate PLD activity and are implicated in constitutive vesicular traffic, we have investigated whether ARF is also required for GTP-dependent secretion in HL60 cells. RESULTS: We have used a cell-permeabilization protocol that allows HL60 cells to become refractory to stimulation with GTP gamma S plus 10 microM Ca2+ with regard to secretion and PLD activity. Permeabilization with streptolysin O for 10 minutes permitted the loss of freely diffusable cytosolic proteins, including ARF proteins. Fractions derived from brain cytosol, enriched in ARF proteins, restored secretory function and PLD activity. The major contaminating protein present in these ARF-enriched fractions was identified as phosphatidylinositol transfer protein (PITP). Unexpectedly, PITP was also found to restore GTP gamma S-dependent secretion. Restoration of secretory function was characterized using recombinant proteins, rARF1 and rPITP alpha and rPITP beta. The rARF1 protein restored both secretory function and PLD activity, whereas PITP only restored secretory function. However, both ARF and PITP were capable of stimulating phosphatidylinositol bis phosphate (PIP2) synthesis. CONCLUSIONS: ARF and PITP restore secretory function in cytosol-depleted cells when stimulated with GTP gamma S plus Ca2+. We have previously shown that PITP participates in the synthesis of PIP2. In comparison, ARF1 activates PLD, producing PA, which is a known activator of phosphatidylinositol-4-phosphate 5 kinase, the enzyme responsible for PIP2 synthesis. We propose that ARF and PITP both restore exocytosis by a common mechanism-promoting PIP2 synthesis.

Four beams evanescent waves interference lithography for patterning of two dimensional features.

This work presents a theoretical study of using the interference of multiple counter-propagating evanescent waves as a lithography technique to print periodic two dimensional features. The formulation of the three dimensional Cartesian space expression of an evanescent wave is presented. In this work, the evanescent wave is generated by the total internal reflection of a plane wave at the interface between a incident dielectric material and a weakly absorbing transmission medium. The influences of polarization, incident angle and the phase shifting of the incident plane waves on the evanescent wave interference are studied. Numerical simulation results suggest that this technique enables fabrication of periodic two dimensional features with resolution less than one third the wavelength of the irradiation source.

Use of fluorescein as a ground water tracer in brackish water aquifers.

A drift and pumpback experiment was conducted in a brackish water sandfill. The sandfill was reclaimed from the sea in the eastern part of Singapore and contains sands with low organic and clay/silt contents. The high salinity in the ground water precludes the use of chloride and bromide as tracers in such an environment, and a field experiment was conducted to assess the viability of using fluorescein as a tracer in brackish water aquifers. Nitrate was used as a second tracer to serve as a check. Initial laboratory studies showed that fluorescence was unaffected over the range of electrical conductivity and pH of the ground water. Results from the field experiment show that fluorescein appears to behave conservatively.

Kimura's disease: a diagnostic and therapeutic challenge.

INTRODUCTION: Kimura's disease (KD) is a rare, benign, chronic inflammatory disease with unknown aetiology. Its manifestation is protean. KD has a predilection for the head and neck area, and typically presents as tumour-like lesions that could be easily misdiagnosed. We review our experience with four recent cases. METHODS: Over a four-year period, all patients admitted to Singapore General Hospital with KD of the head and neck region were retrospectively reviewed. Biodata, presenting symptoms and clinical parameters, especially serum eosinophil levels, preoperative investigations, type of surgical procedures and outcome were documented. RESULTS: Four patients presented with KD of the head and neck and displayed varied manifestations of the disease. All the patients had raised serum eosinophil levels. None of them had renal involvement. Preoperative computed tomography were performed in two of the patients and showed features suggestive of KD. Fine-needle aspiration cytology that was performed in two patients was not useful in the diagnosis. All the patients underwent surgical excision of the lesions. Only one patient had multiple recurrence, both at the original and remote sites in the head and neck. CONCLUSION: The clinical presentation and behaviour of KD is very variable. Preoperative imaging is useful in the diagnosis of the disease but the final diagnosis is histological. Surgical excision is the current treatment of choice but recurrence is common. A high index of suspicion and awareness is vital in the early diagnosis and management of KD.

Differential effect of age on transforming growth factor-beta 1 inhibition of prolactin gene expression versus secretion in rat anterior pituitary cells.

Transforming growth factor-beta 1 (TGF-beta 1) synthesized in the pituitary may act as an autocrine/paracrine regulator of lactotrope function. We examined the effects of TGF-beta 1 on PRL messenger RNA (mRNA), PRL synthesis, and PRL secretion in cultured anterior pituitary (AP) cells from rats at different ages. APs excised from ovariectomized female Sprague-Dawley rats, either young(2-3 months old; average serum PRL: 9 ng/ml), middle-aged (11-12 months old; average serum PRL: 133 ng/ml), or old (24 months old; average serum PRL: 159 ng/ml), were dispersed and cultured for 5 days. Then, cells were washed and challenged with increasing doses of TGF-beta 1 (0-100 ng/ml) for 1-48 h in serum-free medium. Northern blot analysis showed an increase in basal PRL mRNA levels, and a decrease in responsiveness to TGF-beta 1 with age. TGF-beta 1 suppressed PRL mRNA in a dose- and time-dependent manner in cells from young rats. Maximum inhibition was observed at 0.5-1 ng/ml of TGF-beta 1. At 0.5 ng/ml TGF-beta 1, significant reduction in PRL mRNA was detected at 6 h, and maximum inhibition was observed at 12-48 h post TGF-beta 1 incubation. Cells from middle-aged rats were less responsive to TGF-beta 1, whereas cells from old rats did not seem to respond under our experimental conditions. In addition to its effect on PRL mRNA in young AP cells, TGF-beta 1 dose dependently inhibited the rate of PRL synthesis, as indicated by reduced [35S]methionine incorporation into immunoprecipitated PRL. Responsiveness of PRL synthesis to TGF-beta 1 inhibition also decreased with age; however, significant inhibition by TGF-beta 1 on PRL synthesis could still be observed in old AP cells. Analysis by RIA demonstrated that young AP cells produced lower levels (15 micrograms/10(6) cells.24 h) of PRL in culture medium than old AP cells (32 micrograms/10(6) cells.24 h). TGF-beta 1 decreased medium PRL levels in old AP cells as efficaciously as in young AP cells. Significant reduction in medium PRL secreted by young AP cells was observed at 3 h when changes in both PRL mRNA and PRL synthesis were not evident. Taken together, our data suggest that TGF-beta 1 affects PRL production at multiple levels. Moreover, its inhibition on PRL synthesis and mRNA expression, but not on PRL secretion, is age-related. Thus, TGF-beta 1 may play an important role in regulating lactotrope function during aging.

Primary uterine endometrial stromal neoplasms. A clinicopathologic study of 117 cases.

We present the results of a clinicopathologic study of 109 patients with endometrial stromal sarcoma and eight patients with endometrial stromal nodule. Of the 109 patients with endometrial stromal sarcoma, follow-up was obtained on 93 (85%). The stage distribution of the patients with stromal sarcoma and the number of patients with follow-up (numerator) compared to the total number of patients in each stage (denominator) are: Stage 1, 73/85; Stage II, 3/6; Stage III, 11/11; Stage IV, 6/7. Stage II patients are considered separately in the analysis. Thirty-six percent of the Stage I patients experienced one or more relapses. Of these, six (23%) died of disease from 11 to 360 months from diagnosis (median, 79 months). Nine (35%) were alive with disease. Of the eleven Stage III patients, eight had one or more relapses and of these, six died of disease. Of the six Stage IV patients, five had one or more relapses and of these, three died of disease. The outcome differences between Stages I, III, and IV are statistically significant (p less than .01). Microscopic features evaluated included the mitotic index (MI = number of mitoses/10 high-power fields) and cytologic atypia. Forty-five percent of Stage I patients who had both rare mitotic figures and minimal atypia had one or more relapses and of these, two (13%) died of disease at 85 and 360 months, respectively. Thus, neither MI nor cytologic atypia were predictive of tumor recurrence for patients with Stage I tumors.

Regulation of topoisomerase II expression during the VM-26 induced differentiation of IW32 murine erythroleukemia cells.

The effect of VM-26, a topoisomerase II targeting drug, on IW32 murine erythroleukemia cells was investigated. The VM-26 induced IW32 cells to differentiate at a non-toxic but cytostatic concentration (0.01 microgram/ml). More than 40% of the cells were induced to synthesize hemoglobin, and cells were arrested in G2/M phase of the cell cycle. Levels of beta-globin mRNA also increased significantly. Cells became committed to erythroid maturation after 16 h of continuous drug exposure. Replacement with fresh VM-26 after 48 h of drug treatment further increased the hemoglobin containing cells to greater than 80%. Unlike other drug induced erythroleukemia cell differentiation, c-myc mRNA expression was not affected by VM-26. Inhibition of topoisomerase II activity was observed during the first 12 h of VM-26 treatment; however, elevated enzyme activity was found thereafter. Northern blot analysis showed significant increase in the expression of topoisomerase IIalpha mRNA at 12 and 24 h after VM-26 addition. These findings indicate that VM-26 inhibited the activity of topoisomerase II and promoted the committed differentiation of IW32 cells along the erythroid pathway. In addition, a parallel increase in mRNA and activity levels of topoisomerase II in differentiated cells suggests that regulation of the enzyme expression occurred in the VM-26 induced erythroid maturation.

Diagnostic sensitivity of polymerase chain reaction and Southern blot hybridization for the detection of human papillomavirus DNA in biopsy specimens from cervical lesions.

Human papillomaviruses (HPVs) are associated with benign and malignant neoplasms of the cervix. One of the criteria for their etiologic role requires an assessment of whether virtually all or only a small fraction of lesions contain viral genomes. DNA preparations from colposcopically directed punch biopsies of cervical lesions were analyzed by Southern blot hybridization and the polymerase chain reaction (PCR) for the presence of HPV DNA. The biopsy specimens represented different pathologic entities (koilocytosis, condyloma, cervical intraepithelial neoplasia, and invasive carcinoma). In Southern blot hybridization with radioactive probes for HPV 11, 16, 18, 31, and 33, HPV DNA was detected in 74% of the biopsy specimens (42 of 57 cases), with the predominant types being HPV 16 and HPV 18. In contrast, after PCR amplification with primers yielding fragments of characteristic size for HPV 11, 16, and 18, the analysis of the same 57 biopsy specimens revealed that all samples were positive for at least one HPV type. To exclude false-positive PCR results, controls without HPV DNA were interspersed at regular intervals, and results were evaluated only if these controls remained HPV negative. To exclude false-negative results due to failure of the reaction, a target sequence within the c-Ha-ras-1 gene was used as an internal control. All HPV typing results obtained by Southern blot hybridization were in agreement with HPV typing by PCR. The higher number of positive samples in the latter analysis stems from the increased sensitivity of PCR, which was which was effective in identifying as few as 10-100 HPV DNA molecules; in contrast, the sensitivity of Southern blot hybridization was 1 pg, or approximately 10(5) molecules of HPV DNA. The authors conclude that, with sufficiently sensitive diagnostic methods, HPV DNA can be detected in most, if not all, neoplastic cervical lesions.

Ovarian cystectomy for serous borderline tumors: a follow-up study of 35 cases.

We have investigated the frequency of persistence or recurrence of tumor in 35 patients with ovarian serous borderline tumors treated by unilateral cystectomy, bilateral cystectomy, or unilateral cystectomy with contralateral oophorectomy or salpingo-oophorectomy. Nineteen of the patients had stage Ia, ten had stage Ib, four had stage Ic, and two had stage III tumors. Tumor persisted or recurred only in the ovary that had been subjected to cystectomy in two (6%) of the 33 patients with stage I tumors, in both the ipsilateral and contralateral ovary in one patient (3%), and in the contralateral ovary only in one patient (3%). The frequency of ipsilateral persistence or recurrence of tumor per ovary subjected to cystectomy in this group of patients was 8%. Both patients with stage III tumors had persistence or recurrence of their tumors. Involvement of the resection margin of the cystectomy specimen and the removal of more than one cyst from an ovary were almost always associated with persistence or recurrence of tumor. Follow-up of the 35 patients showed that despite the occasional complication of persistence or recurrence of tumor, all were alive without evidence of disease 3-18 years after the initial operation, with an average follow-up of 7.5 and a median follow-up of 6.5 years.

Human papillomavirus in dysplasia and carcinoma of the cervix in Singapore.

A prospective study was conducted in Singapore in 1985 where 107 women with abnormal cervical smears were studied for cervical neoplasia and its association with the human papillomaviruses (HPV), using HPV 11, 16 and 18 DNA as probes. Cervical biopsies were performed for histology as well as for DNA Southern Blot hybridization studies to detect the presence of HPV 11, 16 or 18 genome. The prevalence of the various types of papillomavirus DNA in cervical tissue samples from cervical carcinoma and dysplasias is presented. HPV types 16 and 18 were found in 5 of 8 (63%) cases of invasive squamous cell carcinoma (SCC), in 12 of 41 (29%) cases of squamous carcinoma-in-situ (CIN 3) and in 3 of 48 (6%) cases of lower grade dysplasia. None of our cases of SCC were associated with unknown HPV types detected using a mixture of HPV 16 or 18 DNA under conditions of low stringency. These unknown HPV types were present in approximately one quarter of our cases of dysplasia of all grades.

Subclinical human papillomavirus infection of the male lower genital tract: colposcopy, histology and DNA analysis.

In 25 partners of women with genital human papillomavirus (HPV) infection or cervical intraepithelial neoplasia, colposcopic examination revealed the existence of subclinical HPV infection of the male lower genital tract in 22 cases. It manifested either as short papillae tipped with acetowhite changes, or flat acetowhite lesions on the foreskin, glans, periurethral region, scrotum, perineum and/or perianal region. Multiple lesions involving several anogenital areas were common. Some of these abnormalities were small and inconspicuous. Of these 22 cases, 17 had histological evidence of HPV infection. Although Southern blot hybridization detected HPV DNA in only one case, polymerase chain reaction (PCR) analysis revealed HPV DNA in 20 cases. There were 10 cases of HPV 16. Subclinical HPV disease is best identified by colposcopy and confirmed by PCR. In treating HPV disease, colposcopic recognition of subclinical HPV disease forms an essential part of the management plan.