Successful treatment of failed AID cases by use of gamete intra-fallopian transfer using donor semen (GIFT (D)).

Over a 13-month period in a newly opened assisted conception unit at the Women's Hospital, Liverpool, gamete intra-fallopian transfer using donor semen, GIFT (D) was offered to eighteen couples who had failed to conceive after numerous cycles of treatment with artificial insemination by donor semen (AID). The indication for the use of donor semen was either azo- or severe oligoaesthenospermia, and, in addition, the female partners have been exhaustively investigated with no major cause found to account for the couple's infertility. Using a basic clomiphene citrate and human menopausal gonadotrophin protocol it was possible to achieve a pregnancy rate of 56% per GIFT (D) cycle. As a consequence of these results it is now our policy to treat couples whose infertility is due to an unresolvable male factor with AID for 12 cycles only. If they have been unsuccessful in achieving a pregnancy after this time, they are offered GIFT (D).     

Direct assessment of the role of NK cells in autoimmune diabetes.

Considerable indirect evidence implicates participation of natural killer cells (NK) in the pathogenesis of diabetes in BB rats. The most convincing evidence derives from studies showing that anti-CD8 antibody effectively prevents both primary disease onset and autoimmune damage to transplanted islets. However, anti-CD8 treatment depletes both NK and cytotoxic T cells (CTL) since both cell types express the CD8 marker. To study directly the role of NK in diabetic BB rats we used MCA 3.2.3, a monoclonal antibody which selectively depletes normal Lewis rats of NK cells but not CTL. A regimen of ip injected antibody achieved rapid reduction of NK cells in diabetic and nondiabetic BB rats by FACS analysis. NK cell activity remained low in rats treated weekly as evidenced by YAC tumor cell killing. We next studied the effect of NK depletion on disease incidence in diabetes-prone BB rats of which about one half are expected to develop diabetes. Onset and incidence of diabetes in 3.2.3-treated and control antibody-treated aged matched litter mates were equal. These studies suggest that NK cells are not necessary for autoimmune islet destruction in spontaneously diabetic BB rats and support a role for CTL in pathogenesis of the disease.     

VASCULAR COMPLICATIONS OF ELECTIVE LOWER LUMBAR DISC SURGERY

Lower lumbar disc surgery is an extremely common operation from which vascular complications are reported rarely. However vascular injury can occur with perforation of the anterior longitudinal ligament. External haemorrhage is uncommon and the true cause of the patient's hypotension may be misdiagnosed. If the hypotension is severe or prolonged laparotomy is indicated, to prevent exsanguination and to effect a repair of the vascular injury. Alternatively, if the injury is missed, an arteriovenous fistula may develop; this diagnosis may be delayed for months or years. One case of severe haemorrhage following lower lumbar disc surgery is reported and a further 69 cases of similar arterial injury have been reviewed from the world literature.     

Implications of sub-specialisation on the waiting times of general surgical clinics.

INTRODUCTION: Controversy around sub-specialisation in a district general hospital (DGH) has been ongoing for years. AIM: To study the effect of colorectal sub-specialisation on general surgical cases. METHODS: A retrospective audit between October 2002 and September 2003, including all referrals to the outpatient clinics of a single consultant surgeon in a DGH. RESULTS: 1,055 patients were seen in outpatient clinics, of which 53% (563) were seen in rapid access colorectal clinics. Overall, 87% (914) of patients were diagnosed to have colorectal pathology. The majority of the colorectal cases were referred using the designated referral forms. There were 427 urgent, 162 soon and 325 routine referrals with colorectal pathology, and 35 urgent, 22 soon and 84 routine referrals with non-colorectal pathology. Median waiting times for urgent, soon and routine referrals were 12, 61 and 91 days, respectively, for patients with colorectal pathology, in comparison with 44, 75 and 397 days for non-colorectal pathology. CONCLUSION: This audit confirms that colorectal sub-specialisation has resulted in a significant delay in the management of patients with non-colorectal diseases. This has major implications within a DGH setting.     

Predictors of punding in Parkinson's disease: results from a questionnaire survey.

Dopamine replacement therapy (DRT) for Parkinson's disease (PD) has recently been linked to the development of a number of nonmotor behavioral control problems. Punding, one of these nonmotor problems, is a term used to describe complex, purposeless stereotyped behaviors such as the repetitive handling or sorting of objects. A self-report questionnaire was adapted to assess punding in the context of dysfunctional hobby-related activities. We report the results of a survey of PD outpatients from a PD research clinic (n = 141) and non-PD controls (n = 103); conducted to identify clinical and psychological factors predictive of punding behaviors. The PD group reported hobbies and activities, which scored significantly higher on the Punding Scale than controls. Higher impulsivity, poorer disease-related quality of life, younger age of disease onset, and concomitant daily medication dosage from dopamine receptor agonists were independently predictive of higher Punding Scale scores in the PD group. These findings are similar to those seen in dopamine dysregulation syndrome, and provide further evidence for the role of impulsivity and age at disease onset in DRT-related nonmotor behavioral problems in PD.     

V-Y advancement flaps. Reusable flaps for pressure ulcer repair

V-Y advancement modification of skin paddle design for the biceps femoris, tensor fascia lata, transverse lumbar, and gracilis flaps permits readvancement of each of these flaps for recurrent pressure ulcers. Our use of this refinement of these flaps over the past twelve years shows that up to two readvancements of each of these flaps can be done, thus preserving reconstructive options in a patient population prone to pressure ulcer recurrence.     

Reciprocal inhibition of nitric oxide and prostacyclin synthesis in human saphenous vein.

1. Angiotensin II (AII) causes contraction of isolated rings of human saphenous vein, responses that are attenuated by the presence of functional endothelium. In this study, we have investigated the mechanisms controlling the release by AII of two endothelial-derived vasorelaxants, prostacyclin (PGI2) and nitric oxide (NO). 2. Myotropic and biochemical changes were measured in response to AII. The biochemical responses measured were the output of PGI2 (as 6-oxo-PGF1 alpha) and of NO (as cyclic GMP). Inhibitors of cyclo-oxygenase (COX; piroxicam) or NO synthase (NOS; L-NAME), were added to the system to determine the influence of endogenous prostaglandins and NO on both myotropic and biochemical responses. Furthermore, to mimic the effects of endogenous, PGI2 or NO, exogenous forms of these relaxants were added, during inhibition of their endogenous release. 3. Contractions of the rings of saphenous vein in response to AII (1-100 nM) were unaffected by treatment with either piroxicam (5 microM) or L-NAME (200 microM) individually. However, when these two inhibitors were used together, there was an increase in the contractions in response to AII. 4. Biochemical analyses revealed that during stimulation by AII, levels of PGI2 and NO were enhanced when synthesis of the other vasodilator was inhibited, suggesting that endogenous NO inhibits PGI2 synthesis and endogenous, PGI2 or another vasorelaxant PG can inhibit NO synthesis. 5. Exogenous PGI2 (as iloprost) or NO (from glyceryl trinitrate) inhibited the increased output of endogenous NO or PGI2 respectively. 6. These results demonstrate the presence, in human saphenous vein, of a mechanism which ensures that levels of vasodilatation are maintained through a compensatory increase in one relaxant agonist when output of the other is decreased. If present in vivo such a mechanism would be important in maintaining saphenous vein graft patency as both PGI2 and NO are not only vasodilators, but inhibit platelet aggregation and myoinitimal hyperplasia, processes implicated in degeneration of graft function.