Hospital admission rates, length of stay, and in-hospital mortality for common acute care conditions in COVID-19 vs. pre-COVID-19 era.

OBJECTIVES: The impact of COVID-19 upon acute care admission rates and patterns are unknown. We sought to determine the change in rates and types of admissions to tertiary and specialty care hospitals in the COVID-19 era compared with pre-COVID-19 era. METHODS: Acute care admissions to the largest tertiary care referral hospital, designated national referral centers for cardiac, cancer and maternity hospital in the State of Qatar during March 2020 (COVID-19 era) and January 2020 and March 2019 (pre-COVID-19 era) were compared. We calculated total admissions, admissions for eight specific acute care conditions, in-hospital mortality rate, and length of stay at each hospital. RESULTS: A total of 18,889 hospital admissions were recorded. A sharp decline ranging from 9% to 75% was observed in overall admissions. A decline in both elective and non-elective surgeries was observed. A decline of 9%-58% was observed in admissions for acute appendicitis, acute coronary syndrome, stroke, bone fractures, cancer, and live births, whereas an increase in admissions due to respiratory tract infections was observed. Overall length of stay was shorter in the COVID-19 period possibly suggesting lesser overall disease severity, with no significant change in in-hospital mortality. Unadjusted mortality rate for Qatar showed marginal increase in the COVID-19 period. CONCLUSIONS: We observed a sharp decline in acute care hospital admissions, with a significant decline in admissions due to seven out of eight acute care conditions. This decline was associated with a shorter length of stay but not associated with a change in in-hospital mortality rate.

Protective effect of garlic extract against maternal and foetal cerebellar damage induced by lead administration during pregnancy in rats.

BACKGROUND: In spite of its industrial usefulness and varied daily uses, lead (Pb) pollution is a widespread ecological problem that faces the humans in the 21th century. Pb was found to produces a wide range of toxic effects including neurotoxicity especially to the developing and young offspring. Recently, the utilisation of herbal plants has received a significant attention where there has been rising awareness in their therapeutic use; among these is the garlic. In light of the above, the current study is designed experimentally in female pregnant rats in order to investigate the beneficial role of garlic extract in the protection from the maternal and foetal cerebellar damage produced by administration of different doses of Pb during pregnancy. MATERIALS AND METHODS: Positively pregnant female rats were divided into five groups; one control group, two Pb-treated groups (exposed to 160 and 320 mg/kg b.w. of Pb, respectively) and two groups treated with both Pb and garlic (exposed to Pb as previous groups together with 250 mg/kg b.w./day of garlic extract). Treatments started from day 1 to day 20 of pregnancy, where the mother rats of different experimental groups were sacrificed to obtain the foetuses. Pb level in the maternal and foetal blood and cerebellum was estimated by spectrophotometry. Specimens of the cerebellum of different mother and foetal groups were processed to histological and immunohistochemical staining for microscopic examination. RESULTS: The results showed that administration of Pb to pregnant rats resulted in a dose-dependent toxicity for both mothers and foetuses in the form of decrease in maternal weight gain, placental and foetal weights, brain weight and diminished foetal growth parameters, which were prominent in rat's group treated with larger dose of Pb. In Pb-treated rats, Pb level in blood and cerebellum was high when compared with the control group. The histopathological examination of the cerebellum of treated dams and foetuses showed marked alterations mainly in the form of Purkinje cell degeneration and lack of development of foetal cerebellum. Co-treatment of garlic extract along with Pb resulted in a significant decrease in Pb levels as compared with those treated with Pb alone with improvement of the histopathological changes. CONCLUSIONS: This study was useful in evaluating the hazardous effects of uncontrolled use of Pb in general and in assessing the developmental and neurotoxicity of foetuses due to exposure during pregnancy in particular. Co-administration of garlic has beneficial effects in amelioration of Pb-induced neurotoxicity and reversing the histopathological changes of the cerebellum of mother rats and foetuses. (Folia Morphol 2018; 77, 1: 1-15).

Advocating the Use of Absorbable Sutures for Columellar Incisions Following Open Rhinoplasty.

Rapidly absorbable skin sutures have been found to be of use in numerous settings including for the closure of the columellar incision following open rhinoplasty. Its removal does not routinely require trimming, and the sutures tend to fall off with minimal intervention 10-14 days postoperatively. This practice has a good acceptance by patients and utilises less resources in the follow-up period. Level of evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

The beneficial roles of insulin and parathyroid hormones in the treatment of experimentally induced diabetic osteoporosis in female rats: bone mineral density, morphometric and histological studies.

BACKGROUND: Diabetes mellitus (DM) and osteoporosis are two frequent medical conditions with an increasing prevalence in elderly people and are responsible for large number of incurable fractures. This study is designed experimentally in female rats in order to determine whether combined treatment of insulin and parathyroid hormone (PTH) enhances the reversibility of the osteoporotic changes that occurred in streptozotocin (STZ)-induced DM. MATERIALS AND METHODS: In this study, 30 adult female rats aged 3 months were used, they were randomly divided into: control group (6 rats) and diabetes group (24 rats), in which experimental DM was induced by i.p. injection of a single dose of STZ (60 mg/kg/body weight). Diabetic group was further divided into four subgroups (6 rats each): non-treated diabetic, insulin-treated (8-12 units s.c./day of Humalin U-40), PTH-treated (6.0 µg s.c./kg/day) and combined insulin and PTH-treated subgroups. All tested groups were assessed for body weight, food and water consumptions. RESULTS: At the end of the experimental period, the bone mineral density (BMD) was measured for all rats of different groups; then the rats were sacrificed and blood samples were collected for measuring glucose, alkaline phosphatase and osteocalcin levels. Right femora were dissected out and subjected to measurement of diameter of neck and shaft, length of shaft, and weight. Then the femora specimens were processed and stained with haematoxylin and eosin for histological study. The results showed that there was a statistically significant, decrease in BMD, increase in the level of alkaline phosphate, and decrease in the level of osteocalcin in rats in diabetic group compared with other groups; these parameters improved in other groups, especially in diabetes/insulin/PTH group. The rats in diabetic group showed statistically significant decrease in neck and shaft diameters and weight of femur bone compared with other groups, while rats in diabetes/insulin/PTH group showed a significant improvement of these parameters. In diabetic group, there were different histopathological changes in cortical bone and Haversian canals, which improved in other groups, especially in rats in diabetes/insulin/PTH group. CONCLUSIONS: The untreated DM resulted in dramatic reduction in BMD and morphometric parameters. Treatment with insulin ameliorated these effects to some extent, while PTH co--treatment had a more positive effect. The combination of PTH and insulin resulted in stronger improvement of all parameters to approximately like those of control rats.

A feasibility study of using a high-definition intra-operative exoscope in teaching septorhinoplasty.

OBJECTIVE: This pilot study aimed to assess the feasibility of using a high-definition intra-operative exoscope in teaching septorhinoplasty. METHODS: The exoscope was used in septorhinoplasty cases with different trainers and trainees. A high-definition screen displayed real-time, magnified images. Post-procedure, a questionnaire was completed by trainer and trainees, assessing the feasibility, safety and content validity of the exoscope as a septorhinoplasty training tool. RESULTS: Trainees and trainers assigned favourable ratings to all aspects of the exoscope as a training tool, particularly with regard to teaching anatomy and improving visualisation. CONCLUSION: The exoscope is a potentially effective training tool in septorhinoplasty, and is especially useful in improving visualisation, without restricting the operator. Annotatable intra-operative photographs and videos allow trainees to study cases outside of the operating theatre environment. The use of an exoscope for septorhinoplasty in the UK may facilitate increased hands-on involvement earlier in training than is currently typical.

Optimising outcomes in the management of spontaneous cerebrospinal fluid rhinorrhoea.

BACKGROUND: To describe our experience of the management of spontaneous cerebrospinal fluid (CSF) rhinorrhoea in a large case series focusing on surgical approach, peri-operative management and outcomes; to evaluate the efficacy of endoscopic CSF leak repairs. METHODOLOGY: Retrospective chart review was performed for all patients with spontaneous CSF rhinorrhoea managed from 2003 to 2011 at a tertiary referral centre. Data regarding demographics, presentation, site of leak, peri-operative management, surgical approach, body mass index (BMI), follow up and success rates was collated. RESULTS: Thirty-six patients were identified: 9 male and 27 female with a mean age of 50.4 years. Eight patients had previous failed repairs in other units. Success rate after first surgery was 89 % and after second surgery was 100 %. Four patients had recurrences, 3 underwent successful revisions and the fourth had complete cessation of the leak after gastric bypass surgery and weight reduction. All failures were before 2004 prior to instigation of an anatomic three-layered repair with no further failures in the following 7 years. Mean follow up was 21.5 months. Mean body mass index was 34.0 kg/m2. Fifty percent of spontaneous leaks were from the cribriform plate, 22 % sphenoid, 14 % ethmoid and 14 % frontal sinus. CONCLUSION: Endoscopic CSF fistula closure has become the gold standard of care. In order to optimise the outcome, we recommend a multidisciplinary approach to manage the associated idiopathic intracranial hypertension and an anatomic three-layered closure technique for recalcitrant cases.

The role of peripheral ocular length and peripheral corneal radius of curvature in determining refractive error.

PURPOSE: The purpose of this study was to extend the knowledge of peripheral biometric component and its relationship to refractive status in healthy individuals by determining the correlation between peripheral ocular length to peripheral corneal radius ratio and the refractive error. METHODS: This prospective study was conducted on thirty-three healthy adult participants. Refractive error was assessed objectively and subjectively and recorded as the mean spherical equivalent. Central and peripheral ocular lengths at 30° were assessed using partial coherence interferometry under dilation with 1% tropicamide. Central and peripheral corneal radius of curvature was assessed using Scheimpflug topography. Peripheral ocular lengths at 30° were paired with peripheral corneal curvatures at the incident points of the IOLMaster beam (3.8mm away from corneal apex) superiorly, inferiorly, temporally and nasally to calculate the peripheral ocular length-peripheral corneal radius ratio. Descriptive statistics were used to describe the distribution and spread of the data. Pearson's correlation analysis was used to present the association between biometric and refractive variables. RESULTS: Refractive error was negatively correlated with the axial length-central corneal radius ratio (r=-0.91; p<0.001) and with 30° peripheral ocular length-peripheral corneal radius ratio in all four meridians (r≤-0.76; p<0.001). The strength of the correlation was considerably lower when only axial length or peripheral ocular lengths were used. CONCLUSION: Using the ratios of peripheral ocular length-peripheral corneal radius to predict refractive error is more effective than using peripheral corneal radius or peripheral ocular length alone.

Estimating the effect of nasal steroid treatment on repeat polypectomies: survival time analysis using the General Practice Research Database.

BACKGROUND: Intranasal steroids are effective in preventing or delaying recurrence of nasal polyps. However, their effectiveness in delaying a need for repeat polypectomy in clinical practice is unknown. OBJECTIVES: To compare time to a repeat polypectomy between post-polypectomy intranasal steroid users and non-users. METHODOLOGY/PRINCIPLE: Our cohort consisted of patients in GPRD who had undergone at least one nasal polypectomy procedure in or after the year 2000. These patients were followed for up to 4 years and the time to next polypectomy was estimated. Cox`s proportional hazards regression was used to estimate the effect of post polypectomy intranasal steroid treatment on time to the next polypectomy after controlling for other respiratory conditions and their treatment. RESULTS: The cohort consisted of 1,675 patients with a mean age of 59 years and 68% males. Of these, 576 patients were post-polypectomy steroid users and 1,099 patients were steroid non-users. The median time to repeat polypectomy was 812 days among the steroid users and 736 days among steroid non-users. Significantly less proportion of intranasal steroid users experienced a repeat polypectomy compared to steroid non-users. This difference was consistent among subgroups of females and concomitant rhinitis treatments users. Patients with post polypectomy intranasal steroid use showed lower risk for a repeat polypectomy compared to steroid non-users. Concomitant rhinitis medication users showed a higher risk whereas other confounders were not significant. CONCLUSIONS: Intranasal steroids were effective in delaying a repeat polypectomy. However, further research using a prospective design is necessary to quantify the benefit of ongoing steroid treatment.

The menthol and cold sensation receptor TRPM8 in normal human nasal mucosa and rhinitis.

BACKGROUND: Menthol and cold sensation trigger symptoms and reflex responses in the upper airway, but the underlying molecular mechanisms are unknown. We have therefore studied nerve fibres expressing the menthol and cold receptor TRPM8 in normal human mucosa, and in rhinitis. TRPM8 nerve fibres were compared with those expressing other TRP receptors including TRPV1 (capsaicin and heat receptor), and TRPA1 (mechano-cold receptor). METHODS: Immunohistology and image-analysis were used to study TRP receptors in biopsies of nasal turbinate from control subjects, patients with allergic rhinitis, and non-allergic rhinitis. RESULTS: TRPM8-immunoreactive nerve fibres were observed in the sub-epithelium, and were profuse around blood vessels in deeper regions, where they were markedly greater in number than TRPV1+ fibers. Image analysis of TRPM8 in sub-epithelial and vascular regions showed no significant differences between control and the rhinitis patient groups. TRPA1-immunoreactivity was weak and seen rarely in nerve fibres. CONCLUSION: We show that TRPM8 nerve fibres are abundant in nasal mucosa particularly around blood vessels, and may mediate neurovascular reflexes. TRPM8 antagonists deserve consideration for therapeutic trial in rhinitis.

Image guidance removal of a foreign body in the orbital apex.

Retrieval of foreign bodies lodged in the orbit present a challenging surgical problem. The trans-nasal approach when combined with image-guided navigation allows clear identification of structures and increased safety. We report a case of a successful removal of a foreign body under image-guidance using a trans-nasal approach.

Anatomical variation of sciatic nerve division in the popliteal fossa and its implication in popliteal nerve blockade.

The sciatic nerve (SN) originates from the L4-S3 roots in the form of two nerve trunks: the tibial nerve (TN) and the common peroneal nerve (CPN). The TN and CPN are encompassed by a single epineural sheath and eventually separate (divide) in the popliteal fossa. This division of the SN occurs at a variable level above the knee and may account for frequent failures reported with the popliteal block. We studied the level of division of the SN in the popliteal fossa and its relationship to the common epineural sheath of the SN. The level of division of the SN sheath into TN and CPN above the knee was measured in 30 cadaver specimens. The SN was invariably formed of independent trunks (TN and CPN) encompassed in one common epineural sheath. The SN divided at a distance range of 50 to 180 mm above the popliteal fossa crease. The present findings suggest that the TN and CPN leave the common SN sheath at variable distances from the popliteal crease. This finding and the relationship of the TN and CPN sheaths may have significant implications for popliteal nerve block.

The Doyle-Saleh blink reflex.

OBJECTIVES: When performing septoplasty or septorhinoplasty, we have observed that patients blink on injection of local anaesthetic (lidocaine 1 per cent with adrenaline 1:80 000) into the nasal mucosa of the anterior septum or vestibular skin, despite appropriate general anaesthesia. This study sought to quantify this phenomenon by conducting a prospective audit of all patients undergoing septoplasty or septorhinoplasty. METHODS: Patients were observed for a blink reflex at the time of local anaesthetic infiltration into the nasal vestibule. Also measured at this point were propofol target-controlled infusion levels, remifentanil rate, bispectral index, blood pressure, heart rate, pupil size and position, and patient movement. RESULTS: There were 15 blink reflexes in the 30 patients observed. The average bispectral index value was 32.75 (range, 22-50) in the blink group and 26.77 (range, 18-49) in the non-blink group. No patients moved on local anaesthetic injection. CONCLUSION: The blink reflex appears to occur in 50 per cent of patients, despite a deep level of anaesthesia. Without an understanding and appreciation of the blink reflex, this event may result in a request to deepen anaesthesia, but this is not necessary and surgery can proceed safely.

Impact of developing a multidisciplinary coded dataset standard on administrative data accuracy for septoplasty, septorhinoplasty and nasal trauma surgery.

OBJECTIVE: This study aimed to develop a multidisciplinary coded dataset standard for nasal surgery and to assess its impact on data accuracy. METHOD: An audit of 528 patients undergoing septal and/or inferior turbinate surgery, rhinoplasty and/or septorhinoplasty, and nasal fracture surgery was undertaken. RESULTS: A total of 200 septoplasties, 109 septorhinoplasties, 57 complex septorhinoplasties and 116 nasal fractures were analysed. There were 76 (14.4 per cent) changes to the primary diagnosis. Septorhinoplasties were the most commonly amended procedures. The overall audit-related income change for nasal surgery was £8.78 per patient. Use of a multidisciplinary coded dataset standard revealed that nasal diagnoses were under-coded; a significant proportion of patients received more precise diagnoses following the audit. There was also significant under-coding of both morbidities and revision surgery. CONCLUSION: The multidisciplinary coded dataset standard approach can improve the accuracy of both data capture and information flow, and, thus, ultimately create a more reliable dataset for use outcomes and health planning.

Vanilloid receptor type 1-immunoreactive nerves in the rat urinary bladder and primary afferent neurones: The effects of age.

The vanilloid receptor (VR1) is a molecular integrator of various painful stimuli, including capsaicin, acid and high temperature. VR1 protein functions both as a receptor for capsaicin and a transducer of noxious thermal stimuli. In addition, VR1 is well characterised at the terminals of sensory nerves involved in the pain pathway. VR1 is also expressed in a capsaicin-sensitive and peptide-containing sub-population of primary sensory nerves. Indirect immunohistochemistry was used to examine the distribution of nerves immunoreactive (ir) for VR1 in the base of the urinary bladder and in the neurones of the lumbosacral dorsal root ganglia (L1-L2 and L6-S1) of young adult (3 months) and aged (24 months) male rats. Semi-quantitative estimations of nerve densities were assessed and quantitative studies were also used to examine the effects of age on the percentage of VR1-ir dorsal root ganglion neurones. The bladder base in young adults showed dense VR1-ir fibres within the urothelium and in the subepithelium and fibres ranging from sparse to moderate in number in the muscle coat. In comparison to the young animals, the aged rats showed sparse to moderate densities of VR1-ir nerves in the subepithelium and sparse fibres in the muscle layers. In the lumbosacral dorsal root ganglia the percentage of VR1-ir neuronal profiles showed a significant reduction from (mean +/- SEM) 17.8 +/- 2% in the young adult to 12 +/- 1.6 in the aged rats. The present findings suggest that the effects of VR1 on bladder function (nociception and reflex micturition) are influenced by age and the reduction with age of VR1-ir neurones in the dorsal root ganglia could also have important implications for the micturition reflex.

Double seal technique to obliterate the eustachian tube orifice: a novel method for the treatment of recalcitrant cerebrospinal fluid leak.

OBJECTIVE: To demonstrate a novel and effective surgical technique for the treatment of refractory cerebrospinal fluid rhinorrhoea after skull base surgery. The novel surgical technique is described and the findings of a review of relevant world English-language publications are reported. CASE REPORT: A 44-year-old woman, otherwise fit and well, presented with more than a 2-year history of right-sided facial pain. A diagnosis of classical trigeminal neuralgia was made. Surgical treatment was undertaken with a retromastoid suboccipital craniotomy. Post-operatively, the patient showed signs of right-sided cerebrospinal fluid rhinorrhoea which was recalcitrant. In light of a continuous leak and several hospital admissions, a novel technique was performed whereby the eustachian tube orifice was obliterated using an endonasal endoscopic approach. The technique proved to be successful, with no further leakage. CONCLUSION: Endoscopic obliteration of the eustachian tube using a double seal technique is a simple, safe and effective procedure in the treatment of a refractory cerebrospinal fluid leak.

Endometrial unresponsiveness: a novel approach to assessment and prognosis in in vitro fertilization cycles.

OBJECTIVE: To categorize endometrial responsiveness to orally administered estriol in natural cycles of patients with thin endometrium. The value of endometrial responsiveness in predicting the outcome of subsequent IVF-ET cycles was evaluated. DESIGN: Prospective clinical study. SETTING: Miami IVF-ICSI Center, Alexandria, Egypt, a private center. PATIENTS: Forty-two patients undergoing IVF-ET. All had endometrial thickness < or = 7 mm at the time of maximal follicular diameter in natural cycle. INTERVENTION: Estriol was orally administered in subsequent unstimulated cycle. Patients were categorized into responsive and unresponsive groups (those with improved and unimproved endometrial thickness, respectively). Lastly, controlled ovarian hyperstimulation (COH) with or without estriol was started in the IVF-ET cycles. MAIN OUTCOME MEASURES: The endometrial thickness during COH with or without estriol, fertilization, pregnancy, and abortion rates. RESULTS: The responsive group compared with the unresponsive group had a significantly higher rate of improved endometrial thickness, a similar number of oocytes retrieved, a similar fertilization rate, and a significantly higher pregnancy rate. CONCLUSION: Patients with endometrial unresponsiveness to estriol in their natural cycles rarely improve by COH and have a poor pregnancy rate in IVF cycles.

Double oocyte aspiration may be a solution for empty follicle syndrome: case report.

OBJECTIVE: To assess the possibility of salvaging the cycle in a case of empty follicle syndrome by scheduling a second retrieval. SETTING: Miami IVF/Intracytoplasmic Sperm Injection Center, Alexandria, Egypt. It is a private center. PATIENT(S): A 24-year-old female with a 6-year history of primary infertility. Intracytoplasmic sperm injection was performed because of her partner's obstructive azoospermia. No oocytes could be retrieved despite normal ultrasonic and hormonal responses and the presence of 25 mature follicles. INTERVENTION(S): Serum hCG on the day of the first retrieval. A second dose of hCG was given after the first retrieval, and a second retrieval was scheduled 24 hours later. MAIN OUTCOME MEASURE(S): Number of oocytes retrieved, fertilization and cleavage rates, and pregnancy outcome. RESULT(S): Serum beta-hCG level on the day of the first retrieval was 300 IU/mL. Eleven oocytes were retrieved, (7 were metaphase II, 3 fertilized, and 2 cleaved) and two embryos were transferred. No pregnancy resulted. CONCLUSION(S): In a variant of empty follicle syndrome, the cycle could be salvaged by giving another dose of hCG and scheduling another retrieval 24 hours later.

Immunohistochemical expression of bcl-2 and p53 oncoproteins: correlation with Ki67 proliferation index and prognostic histopathologic parameters in colorectal neoplasia.

The bcl-2 oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18) and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly evaluated by MIB 1, a monoclonal antibody to Ki67 proliferation antigen. Mutation of the p53 gene is considered the most common genetic aberration in colorectal cancer. Immunohistochemical (IHC) staining expression of bcl-2, Ki67, and p53 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas. The aim of the study was twofold: (i) to investigate any correlation between MIB 1, p53, and bcl-2 immunostaining expression in colonic adenomas and carcinomas and (ii) to identify any relation between these markers and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angiolymphatic invasion, tumor grade, and differentiation in colon carcinomas. bcl-2 was consistently higher in adenomas than in carcinomas. There were 44 of 56 (78.6%) adenomas and 27 of 52 (51.9%) carcinomas positive for bcl-2 (P = 0.004). The mean Ki67 labeling index (LI) was 30.05 +/- 7.6 and 38.12 +/- 11.01 in adenomas and carcinomas, respectively (P = 0.0001). p53 was significantly higher in carcinomas (35 of 52 [67.3%]) than in adenomas (18 of 56 [32.1%]) (P = 0.0004). Expression of bcl-2 in carcinoma was associated with a lower p53 levels and lower mean Ki67 LI and with favorable histopathologic parameters. Higher p53 and Ki67 values were associated with prognostically poor histopathologic features (differentiation and Duke's stage). We conclude that, in contrast to p53 and Ki67, bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with favorable pathologic parameters. Furthermore, an inverse relation exists between p53 and Ki67, and bcl-2 IHC expression in colonic neoplasia. Evaluation of bcl-2, p53, and Ki67 IHC expression in colonic carcinoma may be of value in predicting the clinical course in these patients.

Fluid phase endocytosis within buccal mucosal cells of alcohol misusers.

The structure of the oral mucosa is now well characterised, although studies on oral epithelial cell function have received less attention. The aims of this study were to see whether endocytosis could be demonstrated in cells from oral smears and if so, to assess the effect of chronic high alcohol intake on such uptake. Buccal mucosal smears were collected from 135 patients (91 non- or social drinkers, and 44 patients with harmful alcohol use). Name, age, sex, and alcohol history (for alcohol problem patients) were recorded. Cell suspensions were incubated in a solution of bovine serum albumin (BSA)-coated fluorescently labelled latex microspheres (0.02 micron diameter) in Ham's F-10 culture medium for 1 h at 37 degrees C as a marker of fluid phase endocytosis. Uptake of microspheres was confirmed by confocal microscopy, and mean endocytosed fluorescence levels determined by flow cytometry. A repeat smear from 11 of the alcohol patients was taken 9-14 days later. Endocytosis was significantly reduced in both male (P < 0.01) and female (P < 0.01) alcohol problem patients compared to controls. Units of alcohol consumed and cigarettes smoked per day did not show a dose-response correlation with endocytosis in the alcohol problem patients. Apparent abstinence from alcohol had no further effect on endocytic uptake at days 9-14. This study shows that normal oral squamous cells removed as buccal smears readily endocytose fluorescent microspheres and that this capacity can be affected by alcohol. Chronic high alcohol intake would appear to down regulate endocytosis in buccal cells even up to 14 days of abstinence. This may have implications for the pathogenesis of oral mucosal disorders in long-term users.

Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia.

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.