Totally extra-peritoneal repair of inguinal hernia by a glove-balloon: technical innovation.

Totally extra-peritoneal (TEP) laparoscopic repair of an inguinalhernia involves the creation of an extra-peritoneal space by blunt dissection or the use of commercial balloons. This new technique demonstrates the use of a device to create this extra-peritoneal space, without the need for any commercial balloons. The extra-peritoneal space was created using a glove-balloon. A total of 107 consecutive TEP repairs were carried out using the glove-balloon technique, these included ten bilateral and 17 recurrent inguinal hernias. This method is simple, cost-effective and easy to teach.     

Social support, social pressures and psychological distress during unemployment

A sample of 1150 unemployed 17 year-olds, containing blacks and whites, males and females, was obtained from 11 urban regions in England. Social support was measured in respect of five different forms of help from others. Measures were also obtained of psychological distress, perceived pressure from others to obtain a job, employment commitment, contact with other young people, and contact with other unemployed young people. Two forms of social support (having someone to turn to for help with money, and having someone to suggest interesting things to do) were significantly associated with measures of distress, as were perceived pressure to obtain a job and employment commitment, but not contact with other unemployed young people. The association between distress and having someone to turn to for help with money was greater for those perceiving pressure from others to obtain a job than those not perceiving pressure. Also, the association between distress and having someone to turn to when feeling low was greater for those with a high employment commitment than for those with a low one. Other associations between support and distress were found to be affected by sex and ethnic differences in the sample. The results are discussed in the light of a stress-buffering model of social support; and the need to disaggregate social support into its component parts is emphasized.     

Carbonic anhydrase gene expression in CA II-deficient (Car2−/−) and CA IX-deficient (Car9−/−) mice

Using real-time PCR and immunohistochemistry, we have examined the expression of carbonic anhydrase isozymes (CA) I, II, III, IV, IX, XII, XIII and XIV in the brain, kidney, stomach and colon of the wild-type, CA II-deficient ( Car2^−/− ), and CA IX deficient ( Car9^−/− ) mice. The expression of Car4, Car12, Car13 and Car14 mRNAs did not show any significant deviations between the three groups of mice, whereas both groups of CA deficient mice showed decreased expression levels of Car1 in the colon and Car3 in the kidney. The Car2 mRNA level was greatly reduced but not completely abolished in all four tissues from the Car2^−/− mice in which no CA II protein was expressed. Sequencing the Car2 cDNA isolated from C57BL6 Car2^−/− mice revealed two nucleotide differences from the wild-type C57BL6 mice. One is a silent polymorphism found in Car2 mRNA from wild-type DBA mice, which is the strain that provided the original mutagenized chromosome. The second change is a mutation that causes prematurely terminated translation at codon 155 (Gln155X). Car9 mRNA and CA IX protein expression levels were up-regulated about 2.5- and 3.6-fold, respectively, in the stomach of the Car2^−/− mice. These results suggest that the loss of function of cytosolic CA II in the stomach of Car2^−/− mice leads to up-regulation of an extracellular CA, namely CA IX, which is expressed on the cell surface of the gastric epithelium.     

The effects in vivo of purified preparations of murine macrophage colony stimulating factor-1, recombinant murine granulocyte-macrophage colony stimulating factor and natural and recombinant murine interleukin 3 without and with pretreatment of mice with purified iron-saturated human lactoferrin

The influence of purified natural colony stimulating factor-1 (CSF-1), purified recombinant granulocyte-macrophage (GM)-CSF, purified recombinant interleukin 3 (IL3) and natural IL3 were assessed in mice that were untreated or pretreated with purified iron-saturated human lactoferrin (LF) in order to first suppress myelopoiesis in the mice. S1/S1d mice responded to recombinant GM-CSF and recombinant IL3 in a manner similar to the response of their +/+ littermates. These 4 factors increased the cycling status of hematopoietic progenitors in vivo. The effects were more noticeable if myelopoiesis was first decreased by LF. The effects do not appear to be due to endotoxin contamination. It cannot be discerned from these studies whether the effects are direct ones on the progenitor cells or indirect ones mediated through growth-factor releasing accessory cells. It is possible that effects can be both direct and indirect.     

The effects of interleukins and other soluble factors on T-lymphocyte colony formation.

When plated in semi-solid media, PHA-stimulated human peripheral blood mononuclear cells (PBMC) form discrete T-cell colonies. By contrast, Sephadex G-10 non-adherent (NA) cells (greater than 96% T lymphocytes) show virtually no clonal growth unless cocultured with soluble factors derived from either normal adherent cells or tumour cell lines. Purified IL-1 was able to initiate colony growth of mitogen-stimulated NA cells; cultures containing 20 U of human IL-1 yielded colony counts that were only slightly less than those with PBMC. In addition, recombinant IL-2, free of measurable IL-1, was able to provide the initiating signal required for clonal expansion. Both recombinant and lymphocyte-derived IL-2 were able to enhance the clonal growth of PBMC. Colony growth could be initiated by supernatants derived from short-term cultures of either monocytic (U937, HL60) or B-cell (Raji, Daudi) tumour cell lines. The abilities of these tumour cell lines to promote clonal responses did not correlate with their contents of either IL-1 or IL-2. By contrast, supernatants derived from either K562 (an erythroleukaemic line) or MOLT 4 (a T-cell lymphoma) cells did not provide the initiating signal.     

A genetic and clinical study of individuals with nonsyndromic retinopathy consequent upon sequence variants in HGSNAT,the gene associated with Sanfilippo C mucopolysaccharidosis

Pathogenic variants in the gene HGSNAT (heparan‐α‐glucosaminide N‐acetyltransferase) have been reported to underlie two distinct recessive conditions, depending on the specific genotype, mucopolysaccharidosis type IIIC (MPSIIIC)—a severe childhood‐onset lysosomal storage disorder, and adult‐onset nonsyndromic retinitis pigmentosa (RP). Here we describe the largest cohort to‐date of HGSNAT‐associated nonsyndromic RP patients, and describe their retinal phenotype, leukocyte enzymatic activity, and likely pathogenic genotypes. We identified biallelic HGSNAT variants in 17 individuals (15 families) as the likely cause of their RP. None showed any other symptoms of MPSIIIC. All had a mild but significant reduction of HGSNAT enzyme activity in leukocytes. The retinal condition was generally of late‐onset, showing progressive degeneration of a concentric area of paramacular retina, with preservation but reduced electroretinogram responses. Symptoms, electrophysiology, and imaging suggest the rod photoreceptor to be the cell initially compromised. HGSNAT enzymatic testing was useful in resolving diagnostic dilemmas in compatible patients. We identified seven novel sequence variants [p.(Arg239Cys); p.(Ser296Leu); p.(Phe428Cys); p.(Gly248Ala); p.(Gly418Arg), c.1543‐2A>C; c.1708delA], three of which were considered to be retina‐disease‐specific alleles. The most prevalent retina‐disease‐specific allele p.(Ala615Thr) was observed heterozygously or homozygously in 8 and 5 individuals respectively (7 and 4 families). Two siblings in one family, while identical for the HGSNAT locus, but discordant for retinal disease, suggest the influence of trans‐acting genetic or environmental modifying factors.     

Recurrent Metastatic Chordoma to the Liver: A Case Report and Review of the Literature

Chordoma is a rare malignant neoplasm derived from notochordal tissue that primarily affects the axial skeleton. Almost 40% of patients have non-cranial chordoma metastases. The most common metastatic sites are the lungs, bones, lymph nodes, and subcutaneous tissue. We present a 52-year female with a history of sacral chordoma presenting with abdominal fullness, early satiety, and a palpable abdominal mass. Abdominal magnetic resonance imaging (MRI) revealed an isolated, highly vascularized, and multilobed liver mass in the left lateral segment. The mass was surgically removed using a clean surgical margin. A histological examination and immunohistochemical staining were consistent with a metastatic chordoma. Two years later, follow-up imaging studies showed a 6.5 × 4.0 × 2.0 cm right liver lesion with multiple lungs, chest wall, pleural, and diaphragmatic lesions. Microscopic- and immunohistochemical staining revealed a recurrent metastatic chordoma. Herein, we present a unique case of metastatic recurrent chordoma in the liver with the involvement of other sites. To the best of our knowledge, no other case of recurrent liver metastasis has been reported.