Surgical challenges and outcomes of rhegmatogenous retinal detachment in albinism.

PURPOSE: To report the outcomes and surgical difficulties during rhegmatogenous retinal detachment (RRD) repair in patients with albinism. METHODS: Retrospective analysis of 10 eyes of 9 patients with albinism that underwent RRD repair was performed. Collected data included demographic details, preoperative examination details, surgical procedure, surgical difficulties, anatomical, and visual outcomes. Outcome measures were retinal reattachment and visual acuity at the last follow-up. RESULTS: Mean preoperative best-corrected visual acuity (BCVA) was logMAR (Logarithm of the Minimum Angle of Resolution) 2.15 (range 0.9-3.0) with preoperative localization of causative break in six eyes. One eye had proliferative vitreoretinopathy grade C1 preoperatively. Four eyes underwent scleral buckling (SB) and six underwent 20G pars plana vitrectomy (PPV) with silicone oil injection. Intraoperative complication as iatrogenic retinal break occurred in four eyes. For retinopexy during vitrectomy, endolaser delivery was possible in three out of six eyes, whereas three eyes had cryopexy. The mean follow-up was 12 months in SB group (range 1-12; median 12 months) and 5.33 months (range 1-12; median 3 months) in PPV group. Among vitrectomized eye, two eyes had recurrence at 3 months with oil in situ. Rest of the eyes had attached retina at last follow-up. Mean BCVA at last follow-up was logMAR -1.46 (range 0.7-2.0) with mean improvement of -0.57 logMAR. CONCLUSIONS: Identification of break, induction of posterior vitreous detachment, and endolaser delivery may be difficult during RRD repair in patients with albinism. The incidence of PVR appeared less in these eyes. Both SB and PPV were efficacious and appear to be good surgical techniques for use in this patient population.

Multiple myeloma: a clinical and pathological profile.

UNLABELLED: Multiple myeloma is a plasma cell neoplasm with a spectrum spanning from localized to disseminated forms, plasma cell infiltration of various organs, plasma cell leukemia and abnormal immunoglobulin chain deposition in the tissues. In the bone marrow, myeloma cells are seen, and vary from mature forms to immature pleomorphic, anaplastic cells. M component is found in the serum or urine in 99% of the patients. MATERIALS AND METHODS: This study included all cases of MM diagnosed at Dayanand Medical College and Hospital, Ludhiana, India from March 2003 to August 2004. Clinical findings were recorded and relevant investigations done. RESULTS: Multiple myeloma comprised 11.1% of all hematological malignancies. The mean age was 58.8 years. Bony pain was the most common presenting complaint. Other findings were anemia, raised serum creatinine levels, high serum lactate dehydrogenase and C-reactive protein levels. Plasmablastic morphology was seen in 60% patients with diffuse marrow involvement being the most common pattern. CONCLUSION: The percentage incidence of Multiple Myeloma, out of all hematological malignancies reported in our study is comparable with other studies as regards to the median age of incidence, male to female ratio, clinical presentation and percentage of M band positivity. However, a higher percentage of our patients had hypercalcemia, higher Serum Lactate Dehydrogenase levels and C -Reactive protein positivity and more lytic lesions. This corresponds with a higher tumor cell burden and a more frequent diffuse pattern of bone marrow involvement in our study group. This could be due to the smaller size of our study group, or due to late referral of patients to our tertiary care hospital.

Thyroid-like cholangiocarcinoma of the liver: an unusual morphologic variant with follicular, trabecular and insular patterns.

We report the case of a 26-year-old woman with a 19 cm malignant hepatic neoplasm with morphological features that closely resembled a follicular thyroid carcinoma. Despite this, it was interpreted as a cholangiocarcinoma due to the absence of a primary thyroid tumor and the lack of thyroglobulin and TTF-1 immunoreactivity by the hepatic tumor. The left hepatic lobectomy specimen showed an encapsulated and multinodular gray-white mass with cystic and hemorrhagic areas. Microscopically, it displayed predominant macro and microfolicullar patterns with focal solid, trabecular and insular areas. The small and distended follicles contained a colloid-like secretion and were lined by low cuboidal cells with scant cytoplasm, round or oval hyperchromatic nuclei with fine chromatin. The solid areas, trabecular and insular structures were similar to those of follicular or papillary thyroid carcinomas. In addition, some of the neoplastic cells had clear nuclei with occasional grooves. The tumor was positive for cytokeratin (CK) 7, CK 19 and CD138, and negative for TTF-1, thyroglobulin, Hepar-1, Glypican-3, alpha-fetoprotein and neuroendocrine markers. A thyroid neoplasm was excluded clinically and by ultrasound and computed tomography. Although, the residual hepatic parenchyma was initially not cirrhotic, the patient eventually developed cryptogenic cirrhosis. The patient received adjuvant chemotherapy and died of metastatic disease 18 months after surgery. The thyroid-like pattern broadens the morphologic spectrum of cholangiocarcinoma.

Haemangiopericytoma of the laryngopharynx.

Haemangioperitytoma is a potentially malignant tumor of the head neck legion but till now none has been reported from the laryngopharynx An interesting case involving a young male patient with mild dysphagia and muffling of voice is reported The clinical course and management is being discussed.

Beta3, a novel auxiliary subunit for the voltage gated sodium channel is upregulated in sensory neurones following streptozocin induced diabetic neuropathy in rat.

In the present study we have used in situ hybridization to examine the changes in mRNA expression of the voltage gated sodium channel subunits beta1 and beta3, which occur in response to streptozocin induced diabetic neuropathy. Under control conditions beta1 mRNA was detected throughout the spinal cord and in large dorsal root ganglion (DRG) Abeta fibres whilst beta3 mRNA was expressed exclusively in the layers I/II and X of the spinal cord and in small DRG c-fibres. Following streptozocin treatment, the expression of beta1 mRNA remained unchanged in both the spinal cord and DRG whilst beta3 message was significantly increased in both the spinal cord and in medium diameter Adelta type DRG neurones. In conclusion, the present study illustrates that the development of the neuropathic pain state is associated with distinct changes in the pattern of beta3 subunit expression and that these changes appear to be specific to the neuropathic pain state induced.

Developmental expression of the novel voltage-gated sodium channel auxiliary subunit beta3, in rat CNS.

1. We have compared the mRNA distribution of sodium channel alpha subunits known to be expressed during development with the known auxiliary subunits Nabeta1.1 and Nabeta2.1 and the novel, recently cloned subunit, beta3. 2. In situ hybridisation studies demonstrated high levels of Nav1.2, Nav1.3, Nav1.6 and beta3 mRNA at embryonic stages whilst Nabeta1.1 and Nabeta2.1 mRNA was absent throughout this period. 3. Nabeta1.1 and Nabeta2.1 expression occurred after postnatal day 3 (P3), increasing steadily in most brain regions until adulthood. beta3 expression differentially decreased after P3 in certain areas but remained high in the hippocampus and striatum. 4. Emulsion-dipped slides showed co-localisation of beta3 with Nav1.3 mRNA in areas of the CNS suggesting that these subunits may be capable of functional interaction. 5. Co-expression in Xenopus oocytes revealed that beta3 could modify the properties of Nav1.3; beta3 changed the equilibrium of Nav1.3 between the fast and slow gating modes and caused a negative shift in the voltage dependence of activation and inactivation. 6. In conclusion, beta3 is shown to be the predominant beta subunit expressed during development and is capable of modulating the kinetic properties of the embryonic Nav1.3 subunit. These findings provide new information regarding the nature and properties of voltage-gated sodium channels during development.

Tissue distribution and functional expression of the human voltage-gated sodium channel beta3 subunit.

This study investigated the distribution of beta3 in human tissues and the functional effects of the human beta3 subunit on the gating properties of brain and skeletal muscle alpha subunits. Using RT-PCR of human cDNA panels, beta3 message was detected in brain, heart, kidney, lung, pancreas and skeletal muscle. Both alphaIIA and SkM1 expressed in Xenopus oocytes inactivated with a time course described by two exponential components representing fast and slow gating modes, while co-expression of human beta3 with alphaIIA or SkM1 significantly increased the proportion of channels operating by the fast gating mode. In the presence of beta3 a greater proportion of alphaIIA or SkM1 current was described by the fast time constant for both inactivation and recovery from inactivation. beta3 caused a hyperpolarizing shift in the voltage dependence of inactivation of alphaIIIA and reduced the slope factor. The voltage dependence of inactivation of SkM1 was described by a double Boltzmann equation. However, SkM1 co-expressed with beta3 was described by a single Boltzmann equation similar to one of the Boltzmann components for SkM1 expressed alone, with a small positive shift in V1/2 value and reduced slope factor. This is the first study demonstrating that beta3 is expressed in adult mammalian skeletal muscle and can functionally couple to the skeletal muscle alpha subunit, SkM1.

Pattern of cancer in Dayanand Medical College & Hospital, Ludhiana (a ten year retrospective study).

A ten year retrospective study was undertaken to ascertain the pattern and incidence of cancer in Ludhiana which is an industrial town with catchment area of Ludhiana consisting of Ludhiana distt., Sangrur, Jalandhar, Hoshiarpur, Faridkot, Ferozepur, Ropar, Kapurthala, some parts of Himachel Pradesh and Haryana. A total number of 56,565 biopsies were received for histopathological examinaiton in 10 years and 4,730 cases of cancer were diagnosed. The incidence of total malignant tumors was 8.36%. Females out numbered males in the incidence of cancer, with male to female ratio being 1:1.09. Most of the cancers were seen in the age group of 41-50 years. In females the two most common cancer sites were breast (21.07%) and cervix (19.4%) while in males hypopharynx--larynx (13.94%) and prostate (9.65%) were the most common sites of cancer.

beta3, a novel auxiliary subunit for the voltage-gated sodium channel, is expressed preferentially in sensory neurons and is upregulated in the chronic constriction injury model of neuropathic pain.

Adult dorsal root ganglia (DRG) have been shown to express a wide range of voltage-gated sodium channel alpha-subunits. However, of the auxiliary subunits, beta1 is expressed preferentially in only large- and medium-diameter neurons of the DRG while beta2 is absent in all DRG cells. In view of this, we have compared the distribution of beta1 in rat DRG and spinal cord with a novel, recently cloned beta1-like subunit, beta3. In situ hybridization studies demonstrated high levels of beta3 mRNA in small-diameter c-fibres, while beta1 mRNA was virtually absent in these cell types but was expressed in 100% of large-diameter neurons. In the spinal cord, beta3 transcript was present specifically in layers I/II (substantia gelatinosa) and layer X, while beta1 mRNA was expressed in all laminae throughout the grey matter. Since the pattern of beta3 expression in DRG appears to correlate with the TTX-resistant voltage-gated sodium channel subunit PN3, we co-expressed the two subunits in Xenopus oocytes. In this system, beta3 caused a 5-mV hyperpolarizing shift in the threshold of activation of PN3, and a threefold increase in the peak current amplitude when compared with PN3 expressed alone. On the basis of these results, we examined the expression of beta-subunits in the chronic constriction injury model of neuropathic pain. Results revealed a significant increase in beta3 mRNA expression in small-diameter sensory neurons of the ipsilateral DRG. These results show that beta3 is the dominant auxiliary sodium channel subunit in small-diameter neurons of the rat DRG and that it is significantly upregulated in a model of neuropathic pain.

Bombesin receptors inhibit G protein-coupled inwardly rectifying K+ channels expressed in Xenopus oocytes through a protein kinase C-dependent pathway.

Although activation of G protein-coupled inward rectifying K+ (GIRK) channels by Gi/Go-coupled receptors has been shown to be important in postsynaptic inhibition in the central nervous system, there is also evidence to suggest that inhibition of GIRK channels by Gq-coupled receptors is involved in postsynaptic excitation. In the present study we addressed whether the Gq-coupled receptors of the bombesin family can couple to GIRK channels and examined the mechanism by which this process occurs. Different combinations of GIRK channel subunits (Kir3.1, Kir3.2, and Kir3.4) and bombesin receptors (BB1 and BB2) were expressed in Xenopus oocytes. In all combinations tested GIRK currents were reversibly inhibited upon application of the bombesin-related peptides, neuromedin B or gastrin-releasing peptide in a concentration-dependent manner. Incubation of oocytes in the phospholipase C inhibitor U73122 or the protein kinase C (PKC) inhibitors chelerythrine and staurosporine significantly reduced the inhibition of GIRK currents by neuromedin B, whereas the Ca2+ chelator, BAPTA-AM had no effect. The involvement of PKC was further demonstrated by direct inhibition of GIRK currents by the phorbol esters, phorbol-12,13-dibutyrate and phorbol-12-myristate-13-acetate. In contrast, the inactive phorbol ester 4alpha-phorbol and protein kinase A activators, forskolin and 8-bromo cAMP did not inhibit GIRK currents. At the single-channel level, direct activation of PKC using phorbol ester phorbol-12, 13-dibutyrate caused a dramatic reduction in open probability of GIRK channels due to an increase in duration of the interburst interval.

Renal amyloidosis--a clinicopathologic study.

A total of 19,075 necropsies and 1169 renal biopsies were scrutinised over a period of 20 years (1973-1992) retrospectively with an aim to study the incidence and pattern of renal amyloidosis in Nair Hospital. A total of 75 cases with amyloidosis were detected, 33 from the necropsy series (0.162%) and 42 from biopsies (3.59%). Secondary amyloidosis was seen in 82.66% and primary amyloidosis in 10.66%. Tuberculosis of various organs was the main cause of secondary amyloidosis (79.03%). Nephrotic syndrome was the common mode of presentation (52%). Besides kidney, which were involved in all cases, the liver, spleen and adrenals were other commonly involved organs at necropsy. Renal failure was the leading cause of death (51.51%). Thioflavine-T proved to be more sensitive technique than other conventional staining methods. The potassium permanganate test is a useful test to distinguish secondary amyloid fibrils from other amyloid fibrils. Abdominal fat aspiration may prove to be specific, sensitive and a routine procedure enabling the early diagnosis of amyloidosis leading to increased incidence of amyloidosis during life than at necropsy.

Anti-convulsant drugs, smoking, and body weights in psychiatric in-patients.

Some anti-convulsant drugs have a calming effect that may potentially be used to reduce cigarette smoking. A cross-sectional study, including all 100 psychiatric in-service patients receiving various anti-convulsant drugs and their age- and sex-matched controls, was done. The intensity of their daily cigarette smoking and their body weights were recorded. Of the patients, 25% were non-smokers. Of the 22 patients on phenytoin, eight were non-smokers as opposed to three in the control group. Two thirds of the phenytoin group patients were either non-smokers, or were nominal smokers. As opposed to this, of the control patients and those on other anti-convulsants, two thirds were either moderate or heavy smokers. The phenytoin group of patients weighed less than the controls (149 v 163 lbs). Valproic acid therapy was associated with a significantly higher body weight and with more smoking. Clonazepam's effect was similar to valproic acid, but carbamazepine did not show any relationship either with smoking or with body weights. Therapy with phenytoin is associated with a lower prevalence and a lower intensity of cigarette smoking, together with lower body weights in psychiatric in-patient population.

An in vitro model for chemical extraction of carbon dioxide via modified peritoneal dialysis.

An in vitro model of a new method for paracorporeal removal of CO2, consisting of modified peritoneal dialysis combined with chemical extraction of predominantly bicarbonate CO2, is presented. The peritoneal cavity was simulated by a bubble oxygenator into which 10% CO2 was diffused. Bicarbonate was initially added, but subsequently regenerated by the system. An insoluble chemical (barium hydroxide lime) was used to precipitate the bicarbonate and produce OH- ions, which prevent the acidosis anticipated with the loss of bicarbonate. CO2 removal was computed from the gas flow rate and CO2 concentration as measured with an infrared analyzer. The rate of CO2 removal was found to be a directly linear function of dialysate flow rate, gas flow rate, and concentration of bicarbonate. The model removed 60 ml/min of CO2, but it is capable of removing more, since the variables affecting CO2 removal are controllable by the observer. This new method can extract bicarbonate CO2 without causing depletion of bicarbonate or requiring an infusion of alkali. It is potentially useful in management of hypercapnic respiratory failure and as an adjunct to "apneic oxygenation" in respiratory distress syndrome.