The rhomboid flap for pilonidal disease

Introduction There have been many surgical techniques described for the treatment of pilonidal sinuses. Recurrent disease causes significant morbidity particularly with time from work. Aim To assess the rhomboid flap's role in promoting one‐stage primary healing in pilonidal disease and to evaluate the morbidity and recurrence. Methods Fifty‐three patients were prospectively recruited of which 27 had previous multiple abscess formation requiring surgical drainage from their pilonidal disease, although none had acute disease at the time of surgery. By using the transposition flap, we were able to obliterate the natal cleft and therefore the rolling action of the buttocks between the cleft in these patients and thereby remove one of the factors involved in pilonidal disease. Hospital stay, healing time, wound infection, wound breakdown and recurrence were noted. Results There were 47 males and 6 females with a median age of 28 years (range 16–64 years). Median follow‐up was 24 months (range 3–36 months). Post‐operative morbidity involved superficial wound infection in 7 (13%) which settled with out‐patient dressings. There were four recurrences (7%), two occurred between the flap and the anal canal, and the other two in the flap margin needing intervention. All the patients healed their wounds and the median healing time was 14 days. Conclusion As this condition affects a predominantly young population causing significant time off from work, we feel that the Rhomboid Flap is useful for difficult cases in that it allows early return to full activity and does not necessitate prolonged postoperative care.     

Effect of rufloxacin on in-vitro proliferation and differentiation of human mononuclear cells.

We investigated the effects of rufloxacin, a new, long acting fluoroquinolone, on the growth and differentiation of human peripheral blood mononuclear cells (MNC) stimulated with T- and B-cell mitogenic agents. Rufloxacin inhibited 3H-thymidine incorporation into MNC stimulated with phytohaemagglutinin (PHA) and pokeweed mitogen (PWM) in a dose-dependent manner. The concentrations of rufloxacin required to inhibit 1/2 maximal proliferation of T- and B-cells were 62 and 33.5 mg/L respectively. Rufloxacin, at clinically achievable serum levels (less than 10 mg/L), was found not to inhibit PHA-induced T-cell differentiation as assessed by IL-2 production, IL-2 receptor expression and the expression of cell differentiation markers (CD4 and CD8). However, higher concentrations of rufloxacin (10 and 50 mg/L) markedly inhibited B-cell differentiation in-vitro as determined by the measurement of immunoglobulin production by MNC stimulated with PWM. The clinical relevance of our in-vitro findings remains to be elucidated.     

Differential effects of exercise and housing condition on murine natural killer cell activity and tumor growth.

Acute exercise and exercise conditioning have been shown to affect the activity of natural killer (NK) cells as well as the growth of experimentally induced tumors in animals. Since psychosocial factors are also known to alter NK activity and tumor growth, isolation, a known psychosocial stressor of mice, was also investigated to see if housing condition could alter exercise-induced changes in NK cell activity and tumor growth. NK cell activity and concentration of asialo GM1 (ASGM1) positive splenocytes were measured in male C3H mice inoculated i.v. with CIRAS 3 tumor cells. Mice were housed individually or in groups of four and trained to run for eight weeks on a rodent treadmill; controls remained sedentary throughout the experimental period. At four weeks into the training protocol, mice were injected with the tumor cells and continued to run for four weeks after tumor exposure. There was a significant effect of physical activity (p less than 0.019) but not of housing on splenic NK cytotoxicity against tumor targets in vitro. When the data were analyzed by presence or absence of lung metastases, only those animals without visible lung tumors had significantly higher NK activity as a function of exercise relative to sedentary controls. There were no significant differences in the frequency of ASGM1+ splenocytes between trained and untrained animals, irrespective of presence or absence of lung tumor colonies. There was a significant effect of housing (p less than 0.02), but not of physical activity, in mice with successful tumor takes with greater numbers of group housed animals (29/59) with tumor relative to individually housed animals (13/60).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endometriosis: Endometriosis and infertility: raised iron concentration in the peritoneal fluid and its effect on the acrosome reaction

Endometriosis and infertility are commonly associated. Thisstudy investigated the role of accelerated lipid peroxidationof spermatozoa by the peritoneal fluid of patients with endometriosisas a cause for this association. It proposes that the increasediron concentration present in the fluid of these patients actsas a catalyst for the process. Peritoneal fluid from 25 patientswith endometriosis and 25 matched controls was obtained at laparoscopy.Spermatozoa were incubated in the fluid from both groups andthe subsequent acrosome reaction rates analysed. The relationshipbetween these results and iron concentration in the fluid wasexamined. A significant decrease in the acrosome reaction ratewas seen in the endometriotic group(P = 0.034). Overall, a decreasein the acrosome reaction rate was associated with an increasediron concentration in the fluid(18 of the 25 pairs). In milddisease, (six of 11 pairs), the relationship was not as markedas that in severe disease (12 of 14 pairs). These results suggestthat the peritoneal fluid in patients with endometriosis hasa detrimental action on the acrosome reaction of spermatozoain vitro.     

Nevirapine derivatives with broad-spectrum chemotherapeutic properties for the effective treatment of HIV/AIDS.

A series of nevirapine derivatives has been synthesized in an effort to enhance the spectrum of chemotherapeutic properties for the effective treatment of AIDS and AIDS-related opportunistic infections. The nevirapine derivative bearing isoniazid moiety (3a) was found to be the most potent compound with EC50 of<0.0636 microM, CC50 of>1000 microM and selectivity index of>15,723 which also exhibited 90% inhibition against Mycobacterium tuberculosis at 6.25 microg/ml. Compound 3c showed 100% inhibition against M. tuberculosis and also exhibited potent antibacterial activity against 24 pathogenic bacteria with MIC less than 1 microg/ml.     

Endometriosis and Race

The pelvic findings of 202 infertile women undergoing diagnostic laparoscopy in Kuala Lumpur, Malaysia were compared to that of 464 infertile women undergoing diagnostic laparoscopy in Aberdeen, United Kingdom. Endometriosis was significantly more common in the women from Kuala Lumpur (51% against 22%, p less than 0.001). There was however no significant difference seen in the severity of the disease (AFS Classification, 1985). These findings confirm our clinical impression that endometriosis is more common in Asian women when compared to Caucasian women.     

NMDA receptors regulate developmental gap junction uncoupling via CREB signaling

Signaling through gap junctions (electrical synapses) is important in the development of the mammalian central nervous system. Abundant between neurons during postnatal development, gap junction coupling subsequently decreases and remains low in the adult, confined to specific subsets of neurons. Here we report that developmental uncoupling of gap junctions in the rat hypothalamus in vivo and in vitro is associated with a decrease in connexin 36 (Cx36) protein expression. Both developmental gap junction uncoupling and Cx36 downregulation are prevented by the blockade of NMDA glutamate receptors, action potentials and the calcium-cyclic AMP response element binding protein (CREB), and are accelerated by CREB overexpression. Developmental gap junction uncoupling and Cx36 downregulation are not affected by blockade of non-NMDA glutamate receptors, and do not occur in hypothalamic neurons from NMDA receptor subunit 1 (NMDAR1) knockout mice. These results demonstrate that NMDA receptor activity contributes to the developmental uncoupling of gap junctions via CREB-dependent downregulation of Cx36.     

Mutagenesis studies of the major benzo[a]pyrene N2-dG adduct in a 5'-TG versus a 5'-UG sequence: removal of the methyl group causes a modest decrease in the [G->T/G->A] mutational ratio

The potent mutagen/carcinogen benzo[a]pyrene (B[a]P) is metabolically activated to (+)-anti-B[a]PDE, which induces a full spectrum of mutations primarily at the G:C base pairs (e.g. GC-->TA, GC-->AT, etc.). Each of these mutations can be induced by its major adduct [+ta]-B[a]P-N(2)-dG, where DNA sequence context appears to influence both the quantitative and qualitative pattern of mutagenesis. We noted previously that 5'-TG sequences tend to have a higher fraction of G-->T mutations for both [+ta]-B[a]P-N(2)-dG and (+)-anti-B[a]PDE in comparison with 5'-CG, 5'-GG or 5'-AG sequences. To investigate a possible structural element for this trend, the role (if any) of the methyl group on the 5'-T is considered. Using adduct site-specific means, the [G-->T/G-->A] mutational ratio for [+ta]-B[a]P-N(2)-dG is determined to be approximately 1.08 in a 5'-TGT sequence, and approximately 0.60 in a 5'-UGT sequence. (G-->C mutations are minor.) Although this modest approximately 1.8-fold decrease in [G-->T/G-->A] ratio is statistically significant (P = 0.03), it suggests that the methyl group on the 5'-T is not the main reason why a 5'-T tends to enhance G-->T mutations. This study was prompted by an adduct conformational hypothesis, which predicted that the removal of the methyl group in a 5'-TG sequence would lower the fraction of G-->T mutations; however, the approximately 1.8-fold decrease is too small to do additional experiments to assess whether this conformational hypothesis, or other hypotheses, are the true cause of the decrease, which is discussed in this paper.