Issam M. Francis

Phlorizin Prevents Glomerular Hyperfiltration but not Hypertrophy in Diabetic Rats

The relationships of renal and glomerular hypertrophies to development of hyperfiltration and proteinuria early in streptozotocin-induced diabetes were explored. Control, diabetic, phlorizin-treated controls, and diabetic male Fischer rats were used. Phlorizin (an Na+-glucose cotransport inhibitor) was given at a dose sufficient to normalize blood glucose. Inulin clearance (Cinulin) and protein excretion rate (PER) were measured. For morphometry, kidney sections were stained with periodic acid Schiff. At one week, diabetes PER increased 2.8-folds (P < .001), Cinulin increased 80% (P < .01). Kidney wet and dry weights increased 10%–12% (P < .05), and glomerular tuft area increased 9.3% (P < .001). Phlorizin prevented proteinuria, hyperfiltration, and kidney hypertrophy, but not glomerular hypertrophy. Thus, hyperfiltration, proteinuria, and whole kidney hypertrophy were related to hyperglycemia but not to glomerular growth. Diabetic glomerular hypertrophy constitutes an early event in the progression of glomerular pathology which occurs in the absence of mesangial expansion and persists even after changes in protein excretion and GFR are reversed through glycemic control.

Cysticercosis: imported and autochthonous infections in Kuwait

Intracerebral and non-central nervous system (non-CNS) cysticercosis caused by the larval pork tapeworm Taenia solium was diagnosed in patients in an Islamic state. The mode of transmission and challenges in diagnosis are highlighted. Sixteen patients with neurocysticercosis and six with non-CNS lesions were diagnosed by imaging studies (computerized tomography [CT]/magnetic resonance imaging [MRI]) and serology (ELISA and/or enzyme-linked immunoelectrotransfer blot assay [EITB]). Four of 55 family members, including servants, tested for antibodies were positive by the EITB and ELISA. Only one of these sera tested for antibodies to adult T. solium was positive: that of the cook, the probable source of the infection. We postulate a similar mode of transmission in the other Kuwaitis. Evaluation of several commercially available ELISA kits showed they were of poor specificity. Even in countries where pork consumption is proscribed by religious laws, physicians should include cysticercosis in their differential diagnosis in patients with neurological symptoms or non-CNS lesions, especially in non-endemic countries with a large expatriate population such as Kuwait. In children particularly, and in this region, suspected tuberculous lesions on CT must be investigated to rule out cysticerci by a more diligent use of the sensitive and specific EITB assay. Failure to understand the local epidemiology leads to empirical, inappropriate and prolonged therapy for chronic disease.

Cytomorphological spectrum in scar endometriosis: a study of eight cases

Objective:  Endometriosis due to ectopic endometrial tissue that responds to hormonal stimulation and is extremely rare in a surgical scar appearing in 0.1% of women who have undergone Caesarean section. Fine needle aspiration cytology (FNAC) can be a valuable diagnostic aid in the evaluation of these subcutaneous abdominal masses.

Value of radiologically guided fine needle aspiration cytology (FNAC) in the diagnosis of spinal tuberculosis: a study of 29 cases

FNAC is a simple diagnostic tool for the initial evaluation of various deep seated pathological lesions. This study describes the applicability and practical aspects of the technique in establishing the diagnosis of spinal tuberculosis (TB) with the aid of radiographic guidance. The study was conducted in a major teaching hospital in Kuwait between the years 1985 and 1994. Twenty‐nine patients (M:F = 18:11 and age range 8–72 years) with clinically and/or radiologically suspected spinal TB were seen in the Department of Cytology, Mubarak Al Kabeer Hospital. The patients were re‐examined by either computed tomography (CT) scanning (n = 19) or fluoroscopy (n = 10) to localize the lesion for FNAC. FNAC smears were routinely stained with Papanicolaou and Diff Quik stains and one smear of each case was stained with Ziehl–Neelsen (Z‐N) stain for acid‐fast bacilli (AFB). Aspirated purulent material or syringe washings of dry aspirates were also submitted for microbiological cultures including AFB. Radiological and cytological findings were recorded in each case. Radiological findings included: bony rarefaction and destruction (93.1%), narrowed disc space (89.7%), soft tissue calcification (65.5%) and para‐vertebral abscess formation (51.7%). Cytological findings included: epithelioid cell granulomas (89.7%), granular necrotic background (82.8%) and lymphocytic infiltration (75.9%). Smears were positive for AFB in 51.7% of cases. A positive AFB culture was obtained in 82.8% of cases, including all cases with positive AFB on smear by Z‐N stain. Radiologically guided FNAC with AFB culture is a simple, reliable and practical approach to diagnosing spinal TB lesions. With a high diagnostic yield, it allows immediate initiation of specific treatment, helps to avoid invasive diagnostic procedures, and decreases hospitalization time.

Heat-shock protein 72/73 and impaired wound healing in diabetic and hypercortisolemic states.

BACKGROUND Impaired wound healing is a well-documented phenomenon in experimental and clinical diabetes. Emerging evidence favors the involvement of glucocorticoids (GCs) in the pathogenesis of this diabetic complication. Recent data indicated that a heat-shock protein (HSP) with a molecular weight of about 70 kd is expressed in wound healing and it is under the control of the hypothalamic-pituitary-adrenal axis. In view of these findings, the current study was designed to examine the influence of diabetes and the hypercortisolemic state on the expression of HSP 72/73 during wound healing. METHODS Induction of diabetes was achieved by the intravenous injection of streptozotocin at a dose of 55 mg/kg. Subcutaneously implanted polyvinyl alcohol (PVA) sponges were used as a wound healing model. Control and diabetic animals received, respectively, subcutaneous 30-day timed-release pellets of GC (200 mg) and RU 486 (25 mg). Corresponding animals received placebo pellets. Expression of HSP 72/73 within the PVA sponges was assayed with use of Western blotting and immunohistochemical techniques. RESULTS GCs caused a Cushing-like syndrome with weight loss and adrenal atrophy. A pronounced accumulation of constitutive HSP 72/73 was observed in the cytoplasm of various cell types including fibroblasts, macrophages, and endothelium of nondiabetic controls. The PVA sponge contents of HSP 72/73 were decreased as a function of diabetes. A similar phenomenon was seen in control animals receiving high doses of GCs. Partial normalization of the associated hyperglycemic and hypercortisolemic states of diabetes with insulin (hyperglycemia) and the GC receptor block RU 486 (hypercortisolemia) ameliorated the diabetes-related decrease in PVA sponge contents of HSP 72/73. CONCLUSIONS The current study provides evidence that both diabetes and the hypercortisolemic state are associated with a reduction in PVA sponge content of HSP 72/73. An amelioration of these changes was achieved by the institution of RU 486 therapy. Although our data may point to the possibility that the diabetes-related decrease in HSP 72/73 is mediated at least in part by GCs, a confirmation regarding this premise awaits further investigation.

Papillary Thyroid Carcinoma and Its Variants in Fine Needle Aspiration Smears

OBJECTIVE To study the fine needle aspiration (FNA) cytologic features of papillary thyroid carcinoma (PTC) with special reference to its tall cell variant (TCV), which is the most aggressive of the variants. STUDY DESIGN Fifty-four PTC cases were classified into variants, and the frequency of well-known morphologic criteria was determined. Four parameters were quantitatively analyzed based on a study of 200 consecutive neoplastic follicular cells: shape of cells, color of cytoplasm, intranuclear cytoplasmic inclusion (INCI) and nuclear grooves. RESULTS The PTC cases included 6 TCV (> or = 30% tall cells), 8 cases with a significant tall cell component (sig. TCC) having 10-29% tall cells, 17 usual variant (UV), 17 follicular variant (FV) and 6 miscellaneous variants. TCV differed significantly from UV and FV in having a higher tall cell count, higher count of cells with reddish cytoplasm and INCI, and higher frequency of cases with lymphocytic infiltration. PTC (with significant tall cell component [TCC]) differed significantly from TCV with regard to tall cell count and lymphocytic infiltration, from UV with respect to tall cell count and monolayered sheets, and from FV with respect to tall cells, INCI, grooved nuclei, acinar formation, fire-flare appearance and giant cells. CONCLUSION TCV was cytologically distinct from other variants. The biologic behavior of PTC cases with significant TCC, which morphologically seem to be a group intermediate between TCV on the one hand and UV and FV on the other, however, needs to be carefully monitored.

Hodgkin's lymphoma: Diagnostic difficulties in fine-needle aspiration cytology

It is commonly believed that cytodiagnosis of Hodgkins lymphoma (HL) is much easier than that of non‐Hodgkin lymphoma (NHL). However, recognition of certain NHL subtypes with Reed‐Sternberg (R‐S)‐like cells and results of immunohistochemical studies point to the contrary. To study the limitations of cytology in diagnosis of HL, fine‐needle aspiration (FNA) smears of 130 lymphoma or suspected lymphoma cases were reviewed. Initial and reviewed cytodiagnoses were compared with histopathology in 89 cases. Immunocytochemical and immunohistochemical studies were performed in 56 and 59 cases, respectively. Among histologically diagnosed HL cases, definitive cytodiagnosis of HL (initial as well as reviewed) was significantly less frequent than cytodiagnosis of NHL among histologically diagnosed NHL cases (P = 0.0328 and = 0.0001, respectively). On the other hand, cytologically diagnosed HL/NHL cases were significantly more frequent in the former group (P = 0.0001 and = 0.0018, respectively). ALCL and TCRBCL were the two NHL subtypes which created confusion with HL in FNA smears. Twenty‐one cytohistological concordant HL cases and equal number of discordant cases were compared. When compared with discordant group, the patients in concordant group were significantly younger (P = 0.045). Hodgkin/Hodgkin‐like cells and typical R‐S cells were significantly more frequent in FNA smears of the concordant group (P = 0.0478 and = 0.0431, respectively). Immunocytochemical and immunohistochemical studies showed good correlation with histological diagnosis of HL. It is suggested that proper interpretation of cytologic features, together with use of immunocytochemical parameters can help in reducing the margin of error in cytodiagnois of HL. Diagn. Cytopathol. 2009.

High serum prostate‐specific antigen levels in the absence of prostate cancer in Middle‐Eastern men: the clinician's dilemma

To investigate the common causes of total serum prostate‐specific antigen (PSA) values of> 10 ng/mL in an Arab population, as in the USA and Europe the risk of prostate cancer is considered high in men with such PSA levels.

Changing Spectrum of Squamous Cell Abnormalities Observed on Papanicolaou Smears in Mubarak Al-Kabeer Hospital, Kuwait, over a 13-Year Period

Objective: The aim of this study was to determine the incidence of squamous cell abnormalities in cervical cytology in Mubarak Al-Kabeer Hospital, Kuwait, and to document any change in the pattern of these lesions. Materials and Methods: Over a 13-year period (1992–2004), 86,434 cervical smears were studied in Mubarak Al-Kabeer Hospital, Kuwait. Conventional Pap smears were first examined by cytotechnicians and finally reported by cytopathologists. The smears were classified according to the modified Bethesda system. The age of presentation of squamous cell abnormalities in Kuwaiti women was analyzed. Results: Smears from 83,052 (96.09%) patients were found satisfactory for reporting while the remaining 3.9% was unsatisfactory. Atypical squamous cells of undetermined significance (ASCUS) were seen in 1,790 (2.2%) cases, atypical glandular cells of undetermined significance (AGUS) in 630 (0.8%) cases, low grade squamous intraepithelial lesion including human papillomavirus changes (LSIL) in 824 (1.0%) cases, high grade squamous intraepithelial lesion (HSIL) in 189 (0.2%) cases, and carcinoma in 79 (0.1%) cases of which 44 (0.05%) were squamous cell carcinoma. A comparison of average cases/annum during the study period revealed a significant increase in ASCUS from 1.13 to 2.83% (p < 0.001) and AGUS from 0.33 to 1.08% (p < 0.001). However, the percentage of LSIL, HSIL and carcinoma detected in Pap smears remained the same. Conclusion: A significant linear trend (p < 0.001) was observed in satisfactory smears, ASCUS and AGUS over the years. However, no significant change was found in the detection of LSIL, HSIL and carcinoma. A reduction in the age of LSIL/HSIL and an increasing trend in the number of Kuwaiti women over the years was also observed which makes screening of young women essential in Kuwait.

Papillary thyroid carcinoma: evidence for intracytoplasmic formation of precursor substance for calcification and its release from well-preserved neoplastic cells.

Psammoma bodies (PBs) are believed to represent a process of dystrophic calcification over nonviable and dying tissues. Light microscopic and ultrastructural observations suggest that PB formation follows the intracellular assembly of precursor substances and their calcification leading to death of tumor cells and their release. It may also be the result of local secretion of precursor substances like collagen by tumor cells into extracellular space and their calcification. In an earlier reported study, we demonstrated the extracellular localization of various precursor forms of PBs and of irregular calcification in fine‐needle aspiration (FNA) smears of papillary thyroid carcinoma (PTC). In this report, we describe a PTC case with intracellular formation precursor substances for calcification and their release from the well‐preserved neoplastic cells before undergoing calcification. Ultrasound‐guided FNA smears from a small nodule in the left lobe of thyroid in a 40‐year‐old woman revealed a PTC with numerous intracytoplasmic targetoid bodies, which were magenta colored in MGG stain. On their release from the neoplastic cells, these targetoid precursor bodies were found to be forming pools of matrix material, some of which showed evidence of calcification. The cytologic findings were confirmed by histopathology of the tumor in the thyroidectomy specimen. For the first time, we demonstrate through cytomorpholgy the intracytoplasmic formation of targetoid bodies as precursor substances for calcification and their release from well‐preserved cells in PTC. We suggest that the calcification in PTC may not necessarily be taking place over nonviable and dying cells. Diagn. Cytopathol. 2008;36:809–812.