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Objectives The wide spectrum of clinical outcomes to SARSCoV-2 exposure suggests that early immune responses play a pivotal role 1 We aim to describe early, longitudinal, local (nasal mucosal lining fluid) and systemic (peripheral blood) cytokine and cellular immune responses to SARS-CoV-2 in a symptomatic index case and their household contacts with detailed clinical and virological phenotyping We hypothesise that immune responses at symptom onset would correlate with outcomes Methods Participants from the London area are referred to INSTINCT study by general practitioners as suspected, or Public Health England as laboratory-confirmed, cases (ethical review details: IRAS 282820, approved 24 04 2020) Households are visited the day after identification and again on days 7, 15 and 28 Clinical and exposure questionnaires, samples of environment (surface swabs and air);oropharynx (swabs);nasal mucosa (synthetic absorptive matrix) and blood, and daily symptom diaries are collected Samples are analysed by PCR, serology, 20-plex cytokine assay and flow cytometry in institutional laboratories Results The index case was the first SARS-CoV-2 PCR-positive recruit of INSTINCT, confirmed on oropharyngeal swab 5 days after symptom onset Contacts 1 and 2, the spouse and daughter, became symptomatic 2 days after the index case and were confirmed PCR-positive 3 days after symptom onset The three PCR-positive individuals seroconverted during follow-up Contact 3, the son, remained asymptomatic, PCRand serology-negative throughout (figure 1a-b) None required hospitalisation Swabs of the kettle and fridge handles were positive for virus, while other household surfaces and air samples were negative Induction, peak and decline of interferonl-1 and IP-10 levels were captured in nasal mucosa, with lower serum levels (figures 1c-f) Conclusion These data demonstrate the ability of the INSTINCT household contact study to capture early immune responses in mild SARS-CoV-2 infection, not captured by COVID-19 hospital cohort studies Early nasal mucosal cytokine responses to SARS-CoV-2 infection are not reflected in serum The correlations observed provide cogent hypotheses that will be tested in the larger INSTINCT cohort, with implications for COVID-19 risk stratification, therapeutics, prophylaxis and vaccinology

The adult hippocampus continuously generates new cohorts of immature neurons with increased excitability and plasticity. The window for the expression of those unique properties in each cohort is determined by the time required to acquire a mature neuronal phenotype. Here, we show that local network activity regulates the rate of maturation of adult-born neurons along the septotemporal axis of the hippocampus. Confocal microscopy and patch-clamp recordings were combined to assess marker expression, morphological development, and functional properties in retrovirally labeled neurons over time. The septal dentate gyrus displayed higher levels of basal network activity and faster rates of newborn neuron maturation than the temporal region. Voluntary exercise enhanced network activity only in the temporal region and, in turn, accelerated neuronal development. Finally, neurons developing within a highly active environment exhibited a delayed maturation when their intrinsic electrical activity was reduced by the cell-autonomous overexpression of Kir2.1, an inward-rectifying potassium channel. Our findings reveal a novel type of activity-dependent plasticity acting on the timing of neuronal maturation and functional integration of newly generated neurons along the longitudinal axis of the adult hippocampus.

This project aimed to investigate the release of mineral N following the ploughing of clover-rich and grass-dominated swards, previously subject either to cutting or grazing regimes. The hypotheses tested were firstly that N mineralisation and losses following incorporation of grass-clover swards are greater than from grass swards, and secondly that N mineralisation and losses following incorporation of previously grazed swards are greater than from previously cut swards. Following ploughing of previously grazed swards in 1992 and swards that had been subjected to an unfertilised, ungrazed regime in 1993, N uptake, N leaching losses (measured by soil solution samplers with drainage estimation from a nearby experiment) and N2O losses (measured by the closed chamber method) were determined on both resown and fallow plots. Results showed: (1) higher N release after ploughing from the grass-fallow treatment (449 kg N ha–1) than from the grass-clover fallow treatment (244 kg N ha–1) over 18 months; (2) the net release of N after ploughing and reseeding, compared with a continued unfertilised sward, was about 85 kg ha–1 for the grass-clover plots and 140 kg ha–1 for the grass-only plots, over the following 18 months. Of this, the net releases in the second cropping season after incorporation were 19 and 25 kg N ha–1 on the resown grass-clover and grass-only plots, respectively; (3) the net release of mineral N after ploughing in 1993/1994, when swards had not been grazed for over a year, was only about 40 kg ha–1 and no effect of the previous sward was evident; (4) in the 7 weeks after the 1992 ploughing, there was a considerable short-term input of N2O to the atmosphere (1.5–3.7 kg N ha–1), due to the supply of readily available C. Leaving swards ungrazed and unfertilised over winter before ploughing in spring has the potential to reduce such emissions considerably. We conclude that N release following cultivation of grazed swards is more a function of grazing intensity and history prior to ploughing rather than of sward composition.

If a thermal disturbance such as a step change in temperature is applied at each surface of a homogeneous slab of thickness 2L, the effect of cooling at x = +L at first has no effect at x = −L but is clearly evident after a time described by a Fourier number F0 = λt/ρcpL2 of around 0.2. To establish the time of a perceptible change the minimum value of φi − (φ1 + (φ2) is sought, where φ1 is the flux into a semi-infinite solid and φ1 and φ2 are the first and second eigenfunction contributions to the solution for a slab of finite thickness. Cooling throughout the slab is determined virtually by the first eigenfunction alone after F0 = 0.22. For a fluid-cooled slab these values are larger.

AIMS: To present experimental evidence in support of a proposed common cause for absorptive hypercalciuria, renal hypercalciuria, renal phosphate leak and enhancement of 1,25-(OH)2-vitamin D concentrations in patients presenting with renal stone disease; and to suggest further investigation with a view to new management. METHODS: An oral calcium loading test was administered to 15 patients with renal stones and 10 normal controls in the fasting state: urine and blood were collected hourly. After the second urine sample, 400 mg calcium dissolved in water was administered orally. Serum calcium, albumin, parathyroid hormone (PTH), and phosphate were measured together with urine calcium clearance and urinary phosphate from which the TmPO4/glomerular filtration rate (GFR) ratio was calculated. Serum 1,25-(OH)2-vitamin D was measured in the first serum sample. In addition, 24 hour urine calcium results were collected retrospectively from the patients' case notes over the previous 18 months. RESULTS: In the basal state, renal stone patients had an overall greater phosphaturia (lower TmPO4/GFR: median 1.72 compared with 2.10 in controls) and increased calcium clearance. Serum corrected calcium and PTH concentrations did not differ between the groups. After calcium loading, serum calcium and urine calcium clearance rose in both groups, with patients with renal stones experiencing a greater percentage fall in phosphaturia. In both groups TmPO4/GFR fell (greater phosphaturia) with increased serum corrected calcium, with the patients showing notably greater phosphaturia for any given calcium concentration. Patients also had notably greater phosphaturia compared with the serum calcium concentration for any given PTH value. Serum 1,25-(OH)2-vitamin D was higher in patients than controls and for any 1,25-(OH)2-vitamin D concentration phosphaturia measured against serum calcium was greater in patients than controls. 1,25-(OH)2-vitamin D did not correlate with phosphaturia relative to serum calcium concentrations within the patient and control groups. CONCLUSIONS: It is proposed that patients with idiopathic hypercalciuria have an "inappropriately' high phosphate excretion for any given serum calcium concentration. Loss of phosphate may induce increased activation of 1,25-(OH)2-vitamin D. Some of the commonly described causes of stone formation may be manifestations of a single mechanism.

SummarySummaryProthrombin fragment F1 + 2 and thrombin-antithrombin complexes (TAT) were measured in 97 postmenopausal women, either untreated or stabilised on subcutaneous depot, oral or transdermal hormone replacement treatment. Thirty-two used depot, 34 transdermal or oral hormone replacement and 31 were untreated. Control, oral or patch and depot groups had mean (± s.d.) Fl+2 levels of 1·25±0·40, 1·13±0·31 and 1·11±0·31 nmol/l, and mean TAT levels of 2·1±0·76, 2·03 20·61 and 1·75±0·63 nmol/l respectively. Oestradiol levels were elevated in both treatment groups compared with controls (P < 0·001). Although oestradiol levels were supraphysiological in 22/32 (62 per cent) of women using depots and 6/19 (32 per cent) of women using oral hormones, no relationship between F1 + 2 and TAT and oestradiol was observed.

Introduction. Uterine rupture is a potentially catastrophic complication of vaginal birth after caesarean section. We describe the sixth case of posterior uterine rupture, with intact lower segment scar, and the first neonatal survival after expulsion into the abdominal cavity with posterior rupture.Case Presentation. A multiparous woman underwent prostaglandin induction of labour for postmaturity, after one previous caesarean section. Emergency caesarean section for bradycardia revealed a complete posterior uterine rupture, with fetal and placental expulsion. Upon delivery, the baby required inflation breaths only. The patient required a subtotal hysterectomy but returned home on day 5 postnatally with her healthy baby.Discussion. Vaginal birth after caesarean section constitutes a trial of labour, and the obstetrician must be reactive to labour events. Posterior uterine rupture is extremely rare and may occur without conventional signs. Good maternal and fetal outcome is possible with a prompt, coordinated team response.

Lisinopril is an angiotensin converting enzyme inhibitor used in the treatment of cardiovascular disease. We report a case of pemphigus foliaceus in a 66-year-old male treated with lisinopril for hypertension and a previous myocardial infarction. The drug-induced variant of pemphigus is caused by a wide variety of drugs and is most frequently associated with captopril and penicillamine. It has not previously been reported in this commonly used drug.

Aims—To investigate whether increasing the daily baseline of gut calcium can cause a gradual downregulation of the active intestinal transport of calcium via reduced parathyroid hormone (PTH) mediated activation of vitamin D, and to discuss why such a mechanism might prevent calcium oxalate rich stones. To demonstrate the importance of seasonal effects upon the evaluation of such data. Methods—Within an intensive 24 hour urine collection regimen, daily calcium supplementation (500 mg) was given to five stone formers for a 10 week period during a six month crossover study. In a further population of patients on follow up for previous renal stone disease, observations were made on 1066 24 hour urine samples collected over five years in respect of seasonal effects relevant to the interpretation of the study. Results—In the group of patients on calcium supplements the following results were found. During calcium supplementation, the proportion of urine calcium to oxalate was higher (increased calcium to oxalate molar ratio), the 24 hour urine product of calcium and oxalate did not rise, and urine oxalate was lower during the first six weeks of supplementation. Twenty four hour urine calcium was 10.2% higher than baseline in the final four weeks of the 10 weeks of supplementation. Twenty four hour urine phosphate was 11.4% lower during the first six weeks of supplementation, but then rose while the patients were still on supplementation; renal tubular reabsorption of phosphate (TmP/GFR) mirrored the urine phosphate changes inversely. PTH was higher after stopping supplementation, but 1,25-(OH)2-cholecalciferol changes were not detected. In the 1066 urine samples collected over five years the following results were found. Calcium and oxalate excretion correlated positively and not inversely. Urine calcium and phosphate excretion were 5.5% and 2.5% higher, respectively, in "light" months of the year compared with "dark" months. A post summer decline in both urine calcium and urine phosphate was relevant to the interpretation of the study. Conclusions—Regular calcium supplementation does not raise the product of calcium and oxalate in urine and the proportion of oxalate to calcium is reduced. The underlying mechanisms of the changes seen in phosphate, calcium, and PTH and the observations on 1,25-(OH)2-cholecalciferol are not clear. Observed changes in phosphate could possibly be part of a calcium regulating feedback loop operating over a period of weeks. In evaluating these mechanisms background seasonal effects are important. It is possible that "programming" of the gut mucosa in terms of calcium transport is a major determinant of the relation between calcium and oxalate concentrations in urine and their relative abundance. Increased oral calcium, in association with a reduction of the relative proportion absorbed, may be pertinent to the prevention of calcium oxalate rich stones. Key Words: renal stones • calcium oxalate product • dietary calcium • renal tubular reabsorption of phosphate

We present the case of a young Caucasian female with a several years' history of left-sided submandibular gland sialadenitis in association with linear unilateral cutaneous lupus erythematosus apparently following the lines of Blaschko. The affected gland was excised and the cutaneous lupus erythematosus was improved considerably by oral Dapsone.

Pure eccrine hamartomas are very rare, and commonly present as localized areas of hyperhidrosis in normal looking skin. We describe a case of bilateral functioning eccrine hamartomas with macroscopically abnormal features in association with Down's syndrome.

Tissue Factor-mediated thrombin generation involves the generation of VIIa and Xa and has been implicated in the pathogenesis of intimal hyperplasia. In experimental vein grafts, Tissue Factor protein is increased over the first 3 days and colocalized with CD18-positive leukocytes; this increase in Tissue Factor precedes the development of intimal hyperplasia. This study further evaluates the potential role of Tissue Factor in vein graft intimal hyperplasia by directly inhibiting Tissue Factor protein.New Zealand white rabbits underwent interpositional bypass grafting of the common carotid artery using the external jugular vein. Perioperatively, murine anti-rabbit Tissue Factor antibody (109 microg/ml gel, 12,500x IC50 of Tissue Factor activity) was applied to the adventitial surface of the graft, using a pluronic gel (30% soln.). Tissue Factor antibody treated vein grafts were compared to control and empty gel-treated vein grafts. Vein grafts were examined at 3 days to assess CD18-positive leukocyte infiltration and the presence of residual antibody by Western blotting. At 28 days, intimal and medial dimensions were quantified using videomorphometry.At day 3, there was marked reduction in CD18-positive leukocytes in the Tissue Factor antibody versus control vein grafts (6.3 +/- 4.7 vs 20.8 +/- 7.4 per 200x field, P0.05). At 28 days, intimal hyperplasia was similar for the control (70 +/- 4 microm, mean +/- SEM), gel (73 +/- 4 microm), and Tissue Factor antibody (75 +/- 4 microm) vein grafts. However, medial thickness (76 +/- 4 microm;, P0.05) was significantly increased compared to the gel treated vein graft (61 +/- 5 microm).Local delivery of pharmacologic doses of an anti-rabbit Tissue Factor antibody decreased CD18-positive leukocyte infiltration but failed to limit intimal hyperplasia in experimental vein grafts. The results suggest that inhibition of Tissue Factor protein modulates polymorphonuclear leukocyte-endothelial interactions but not in the subsequent development of intimal hyperplasia. It implies that the relationship between the extrinsic coagulation cascade and intimal hyperplasia in vein grafts is complex.

BACKGROUND: Intimal hyperplasia remains the leading cause of vein graft failure. Various external stenting devices have been shown to reduce the development of intimal hyperplasia in vein grafts. Mitogenic and mechanotransduction signals are known to be mediated by G protein-coupled receptors. Therefore in this study we examined the alterations in G protein expression and receptor coupling in vein grafts stented with external tube support. METHODS: Thirty New Zealand White male rabbits had a right carotid interposition bypass graft with use of the ipsilateral jugular vein. Fifteen animals received external support and 15 were controls. In a subset the animals either had removal of the external support or a sham-control neck exploration at 14 days after the initial implantation (n = 5 per group). RESULTS: External support reduced G alpha i3 proteins by 30% in vein grafts without changes in G alpha s by Western blot. Vein grafts with external support were significantly less sensitive to pertussis toxin inactivation than controls were in response to both norepinephrine and serotonin. A 24% decrease in intimal thickness was maintained after withdrawal of the initial external support. CONCLUSIONS: The placement of an external support is associated with alternations in G protein expression and receptor coupling function in vein grafts. The results of this study suggest that the development of vein graft intimal hyperplasia may involve G protein-mediated events.

BACKGROUND: Vein graft intimal hyperplasia is associated with changes in G protein expression. The carboxyl terminus of the beta-adrenergic receptor kinase-1 (beta ARKCT) is known to inhibit G beta gamma-mediated mitogen-activated signaling pathways. This study examines the effects of adenoviral-mediated beta ARKCT infection on the development of intimal hyperplasia in vein grafts. METHODS: New Zealand White rabbits underwent bypass grafting of the carotid artery with the jugular vein. Vein grafts were infected with adenoviral vectors encoding for beta ARKCT (n = 19), beta-galactosidase (n = 3), or empty viral constructs (n = 12). In control animals, vein grafting was performed without infection (n = 10). RESULTS: The efficacy of beta ARKCT infection in vein grafts was verified by reverse transcriptase-polymerase chain reaction. X-gal staining of beta-galactosidase-infected vein grafts demonstrated the transgene in cells throughout the vessel wall. Adenoviral infection of vein grafts without gene transfer did not alter wall thicknesses or sensitivities to contractile agonists, compared with control grafts. beta ARKCT infection, however, reduced intimal thickness by 36% (P < .001) and medial thickness by 24% (P < .001), compared with empty viral infection. beta ARKCT-infected vein grafts also demonstrated increased sensitivity in response to contractile agonists. CONCLUSIONS: These results show that inhibition of G beta gamma signaling with adenoviral-mediated beta ARKCT in vivo infection effectively modifies the structural and functional hyperplastic abnormalities in vein grafts.

This study examines the effect of the angiotensin II receptor (type 1) antagonist (L158,809) on the formation of vein graft intimal hyperplasia in vivo, by both localized and systemic administration.Forty New Zealand White rabbits underwent carotid interposition bypass grafting with the external jugular vein and were killed on postoperative day 28. To determine the effect of L158,809 on the development of intimal hyperplasia, 10 animals received long-term oral therapy with L158,809 (10 mg/kg/day, begun 5 days before operation and continued until harvest), 10 animals underwent coating of the grafts with a pluronic gel containing L158,809 (10(-5) mol/L), and 20 animals were controls (10 with and 10 without pluronic gel). These grafts were harvested for either histologic analysis (n = 6 per group) or in vitro isometric tension studies to angiotensin II (n = 4 per group).Long-term oral treatment with L158,809 produced a 43% decrease in intimal thickness from 76 +/- 6 microns (mean +/- SEM) in the control animals to 43 +/- 7 microns in the treated vein grafts (p = 0.002). There was also a significant decrease (44%) in the medial thicknesses between the control (75 +/- 4 microns) and L158,809-treated (42 +/- 6 microns) vein grafts (p = 0.007). The contractile responses to angiotensin II were abolished in the vein grafts by long-term L158,809 therapy. Local application by gel of L158,809 produced a significant decrease (33%) in the intimal thickness (48 +/- 3 microns) but no change in medical thicknesses (76 +/- 6 microns) compared with control grafts. The contractile responses to angiotensin II were unchanged in the vein grafts by local L158,809 therapy.This study shows that a local single application of L158,809 will reduce the intimal response but not the medial response in vein grafts, whereas long-term treatment will reduce intimal hyperplasia and the medial response in experimental vein grafts. Therefore angiotensin II acting through AT1 receptors mediates a significant part of the intimal hyperplastic response in vein grafts that appears to involve two phases: an acute intimal response requiring short-term therapy and a long-term medial response that requires prolonged therapy.

Sweet's syndrome is characterized by tender, red inflammatory nodules or papules, usually affecting the upper limbs, face or neck. It is part of the group of acute neutrophilic dermatoses that includes pyoderma gangrenosum, but can be distinguished by its appearance, distribution and histological features. Four patients with Sweet's syndrome and Crohn's disease are reported. A total of 30 cases from the literature suggest that Sweet's syndrome is an unusual extraintestinal manifestation of either Crohn's disease or ulcerative colitis. There is a strong predilection for women (87%), patients with colonic disease (100%) and those with other extraintestinal features (77%). The rash is associated with active disease in 67-80%, but may precede the onset of intestinal symptoms in 21% and has been reported 3 months after proctocolectomy for ulcerative colitis.

Molecular biology is now a routine tool in almost all biological research fields. With the exponential growth in the number of molecular biological techniques, there is a recognizable need for sensitive, accurate and precise quantitation of nucleic acids. We present here two complementary instruments designed for the quantitation of nucleic acids, the GeneQuant™ II and the DyNA Quant™ 200 Fluorometer. The GeneQuant II can rapidly determine the UV absorbance of a solution and display the calculated DNA, RNA or protein concentration. In addition, the GeneQuant can display calculated melting temperatures for a given DNA oligonucleotide base sequence, a useful feature for primer design. The DyNA Quant 200 quantitates DNA on the basis of the fluorescent Hoechst 33258 dye/double-stranded (ds)DNA assay. Upon binding to dsDNA, the spectral properties of the dye change such that it becomes highly fluorescent at 460 nm when excited at 365 nm. The assay has proven to be a specific and sensitive alternative method for DNA quantitation, particularly for unpurified DNA samples. Together, the GeneQuant II and the DyNA Quant 200 are a cost-effective and convenient solution to the routine protein and nucleic acid quantification needs of the molecular biologist.

The polypeptide VIP has been proposed as an inhibitory nonadrenergic, noncholinergic (NANC) neurotransmitter involved in the relaxation of cavernosal smooth muscle during erection. However, the specific mechanism(s) by which VIP exerts its effect is unknown. To determine whether VIP is involved in NANC-mediated cavernosal relaxation, strips of corpus cavernosum from New Zealand White rabbits were hung in tissue baths; atropine and guanethidine were added to block cholinergic and adrenergic neurotransmission, respectively. The tissue was then submaximally precontracted with norepinephrine (NE) and relaxed by electrical field stimulation (EFS; 10 V square waves, 0.5 msec. duration, 10 second trains at 5, 15 and 40 Hz) before and after preincubation with the VIP antagonist, VIP 10-28. To evaluate the role of nitric oxide (NO) and prostaglandins on the relaxant effect of VIP in the corpus cavernosum, the strips were contracted with NE and subsequently relaxed with cumulative doses of VIP (10(-10) to 10(-6) M.). After VIP dose-response curves were obtained, the strips were preincubated with N omega-nitro-L-arginine (NOARG, an inhibitor of nitric oxide synthase, 10(-4) M.) and the VIP dose-response curve was repeated. Indomethacin (10(-5) M.) was added to one-half of the NOARG treated strips to inhibit prostaglandin synthesis. VIP 10-28 inhibited EFS-induced relaxation (p0.05) and produced dose-dependent relaxation, which was inhibited by NOARG (p0.05). In contrast, the VIP-induced relaxation was more pronounced in the presence of indomethacin (p0.05). Moreover, indomethacin substantially reversed the NOARG inhibition of VIP relaxation (p0.05). These results suggest that VIP is a mediator of NANC cavernosal relaxation and that NO synthesis is involved in VIP-induced NANC relaxation in the corpus cavernosum. In addition, the presence of vasoconstrictive prostanoids modulates this VIP-mediated NANC relaxation. Therefore, VIP appears to contribute to NANC neurally mediated cavernosal relaxation, and its mechanisms of relaxation are dependent on prostanoid and involve the generation of NO.

The characteristic expression of keratins by keratinocytes is well documented. A typical 'hyperproliferative' profile of epidermal keratin expression occurs in psoriasis, wound healing and warts. This study analyses keratin expression in cutaneous lichen planus to determine abnormalities of differentiation occurring in this inflammatory disorder. Using a panel of monoclonal antibodies 28 samples (20 patients) were studied. The results showed that squamous differentiation was unaffected, with keratins K1 and K10 being expressed normally for the site sampled. The main abnormalities included extension of reactivity of the basal cell marker, LH8, into the suprabasal compartment. Keratin K17, usually restricted to adnexal structures, was variably expressed in the basal and suprabasal layers of the interfollicular epithelium of affected epidermis. Keratins K6 and K16, found suprabasally in hyperproliferative states, were detected both basally and suprabasally in all diseased samples. The keratin profile in lichen planus is analogous to the wound healing response. Suprabasal keratin K17 is found in psoriasis, wound healing and viral warts so the changes in keratin K17 may reflect hyperproliferative changes. It is likely that the changes in epidermal keratin expression are due to up-regulation of specific keratin genes by the production of cytokines and inflammatory mediators from the lymphocytic infiltrate typical of lichen planus.

Previous studies in animals and human beings have shown that vein bypass grafts exhibit diminished endothelium-dependent relaxation and the development of intimal hyperplasia. This study examines the effect of L-arginine on experimental vein graft endothelial cell function and the development of intimal hyperplasia.Common carotid vein bypass grafts were performed in 24 New Zealand White rabbits: 12 were controls and 12 received L-arginine (2.25%) orally 7 days before operation and thereafter until harvest 28 days after operation. Intimal and medial dimensions were determined by planimetry on pressure-fixed vessels. Relaxation to acetylcholine, serotonin, calcium ionophore (A23187), and sodium nitroprusside was performed on precontracted vessel rings.Arginine-treated vein grafts showed a 47% reduction in mean intimal thickness (p0.001) compared with controls. By scanning and transmission electron microscopy, all vein grafts showed a confluent endothelium. In contrast to control grafts, which do not relax to acetylcholine and serotonin, arginine-treated vein grafts relaxed in response to both agonists. There was a significant increase (p0.05) in the maximal relaxation to calcium ionophore (A23187) in arginine-treated vein grafts compared with control grafts. Non-endothelium-dependent responses to sodium nitroprusside were equivalent in all vein grafts.This study shows that oral L-arginine supplementation significantly reduces intimal hyperplasia and preserves nitric oxide-mediated relaxation in experimental vein grafts, suggesting a role for nitric oxide in the regulation of the cellular events that lead to intimal hyperplasia.

Hypercholesterolemia is an important contributor to the development of intimal hyperplasia and superimposed accelerated atherosclerosis in vein bypass grafts. This study examines the effect of dietary modification of serum cholesterol on the development of intimal hyperplasia and vasomotor function of vein grafts. Thirty male New Zealand White rabbits had a right carotid vein bypass graft and were put to death 28 days after the operation. Twenty animals received a 1% cholesterol diet for 4 weeks before the operation. In 10 animals this diet was continued until harvest (hypercholesterolemia group). In another 10 animals the diet was changed to standard rabbit chow on the day of the surgical procedure and continued until harvest (cholesterol reduction group). The last 10 animals were control subjects. Vein grafts were harvested either for histologic study or for in vitro isometric tension studies. Cumulative dose response curves to norepinephrine, serotonin, bradykinin, and endothelin-1 were determined. After in situ pressure fixation, intimal thicknesses of the vein grafts were measured by videomorphometry. The change in diet produced a 74% reduction in serum cholesterol concentration within 28 days. There was a 26% reduction in the intimal thickness of vein graft intimal hyperplasia and the macroscopic disappearance of atheromatous lesions from the graft wall, which are always observed in vein grafts from the hypercholesterolemia group. Cholesterol reduction did not change hypercholesterolemia-induced agonist supersensitivity. Therefore, cholesterol reduction slows the formation of intimal hyperplasia in vein grafts but does not prevent the persistence of the hypercholesterolemia-associated smooth muscle phenotype.

The International Missionary Training Hospital is a 340-bed acute general hospital with maternity and paediatric units. It serves a population of 120,000 people within the North Eastern Health Board Area and has approximately 14,000 admissions each year. This report retrospectively reviews the activity of a three bedded, Intensive Therapy Unit (ITU) over the three year period July 1987-June 1990. 805 patients (1.9% of hospital admissions) with an average age of 55 +/- 22 years (mean +/- SD, range 14-94 years) were admitted to the unit. There were 458 males (57%) and 347 females (43%). 68% of the patients were admitted from the general wards and the remainder from the accident unit. 59% of the admissions were immediate postoperative cases. 82% of patients had APACHE scores less than 20. There was a wide diversity of medical and surgical diagnoses requiring treatment. 219 cases required one or more systems to be supported and 586 (73%) were admitted as high dependency cases. For those requiring ventilation, the average ventilation time was 3.2 days (range 0.5-23 days). The average length of stay within in the unit was 2.3 days (range 1-23 days). 86% of the patients were discharged to the wards, 11% died and 3% were transferred to external specialist care facilities. ITU's in district general hospitals serve as both critical care areas and high dependency units. In our opinion they produce a positive contribution to progressive patient care for high risk medical and surgical patients.

Amiotic fluid embolism is still a significant cause of maternal mortality. It must be suspected in all cases of sudden maternal collapse. For successful resuscitation, surgical delivery should be performed without delay.

Despite advances in the design and care of in-dwelling catheters, sepsis remains a significant problem in patients on long-term parenteral nutrition. In recent years there have been a number of reports concerning the successful use of totally implanted subcutaneous venous access devices in the management of patients requiring long-term intermittent intravenous administration of cytotoxic therapy and frequent blood sampling. The use of such a system for the administration of supplementary home parenteral nutrition in a patient with short-bowel syndrome is reported.

Although solar energy has obvious application for heating water in the summer months, its potential for contributing to space heating in the impoverished solar climate of the U.K. winter seems more open to question. St. George's School, Wallasey, 53°25′N was built on the assumption that solar energy could so contribute and the energy is admitted directly into the structure through its large south facing glazed wall. Although supplementary heat has to be supplied, it appears that on this site less such heal is needed in a building in which solar construction is adopted than in an equivalent building of non-solar construction. A large thermal store however must be provided to prevent excessive rises of temperature on sunny days. A thermal model is described to estimate the temperature within the building in the steady state, the daily fluctuating state, and in response to abrupt changes. The estimates are compared with observation. It is concluded that with simple improvements in design, solar energy admitt...

St. George's School, Wallasey, situated in the U.K. at latitude 53.4° N was designed so that equitable thermal conditions should be achieved within it using solar gains, heat from the lighting system and body heat from the children without the use of a conventional heating system. The building opened in 1962 and evoked considerable comment, both favourable and unfavourable, in the mid-sixties. This article briefly notes some of the comments and provides an account of some of the features which the architect incorporated to control the solar gains that enter through the large south-facing solar wall. Later articles in this series describe the findings of observational surveys carried out in the building.

SUMMARY A window with an open south facing aspect can admit large solar gains in cold but sunny conditions and will then reduce the need for back up heating. In cold overcast conditions the same window will cause a bigger demand for heat to be placed upon the heating plant. The net energy need depends upon the local climate, the comfort temperature chosen, ventilation losses and the design of the window or glazed wall. A study is reported in which 50 years of jointly occurring daily values of temperature and irradiance at 53.4°N on a U.K. site are used. A rank order is suggested for the effectiveness of various constructions as energy saving components.

The Wallasey School is now recognized as an important building in the development of passive solar design. This article describes an enquiry into the origins of the building. It reviews such information as could have been known to the architect Mr. E. A. Morgan, at the time he was working on its design, and also discusses briefly such design techniques as are known to have been available to him. Some of his calculations, previously believed to have been associated with the building, are presented in detail. Morgan patented the design and an annotated version is given here. It is concluded that the architect had a good understanding of steady-state heat transfer in buildings but his handling of thermal storage was dubious. There is no direct evidence to suggest that Morgan could be assured that his construction would save, rather than waste, fuel for heating, but attention is drawn to results which indicate that a solar wall in that locality should save energy; Morgan could well have been aware of these findings.

The diffusion of one gas in the stream of another in the annular space between a sleeve gland and a rotating shaft is considered. Experiments are described for finding under what conditions the distribution of concentration of the diffusing gas agrees with that given by simple theory. It is concluded that the theory is inadequate when the shaft runs eccentrically or whirls in the sleeve; the effective length of the gland can easily be halved. An attempt is made to correlate the degree of enhanced back diffusion with the factors causing it.

An observational study on the Wallasey School has demonstrated its ability to maintain in most conditions of climate an equitable indoor climate both in regard to daily mean temperatures and daily variations, through use of solar gain and heat from the lights, and the appropriate control of ventilation. During occupied periods, air temperatures are usually between 17°C in winter and 23°C in sunny summer periods. The room provides a mainly ‘cold wall’ environment. The observational data and a series of model estimates have been compared. The general level of temperature within the building is known to depend strongly on ventilation rate, but since ventilation rate was not measured, steady-state comparisons as such are not possible. The observed and estimated temperature profiles for air and various surfaces including that of the furnishings during a very sunny period are in broad agreement. Analyses of the transient response of the structure in winter conditions has demonstrated a long response time (several days) describing the response of the enclosure, and a shorter response time of about half a day which describes the rate of settlement of internal temperature differences which may be initially present. Evidence is presented indicating low values for the convective heat transfer coefficient. An autocorrelational technique demonstrates that the thermal ‘memory’ of the classroom is much longer in winter than in summer. The response of the room during occupied and unoccupied periods is broadly similar, but conditions are rather more variable during occupation.

Using information on the dimensions and materials of a room in the Wallasey School, estimates are presented of its response to heat inputs due to the lighting system and the sun. The daily variation due to these influences is calculated using transient and harmonic approaches.